Src kinase (Src) is a tyrosine protein kinase that regulates cellular metabolism, survival, and proliferation. Many studies have shown that Src plays multiple roles in macrophage-mediated innate immunity, such as phagocytosis, the production of inflammatory cytokines/mediators, and the induction of cellular migration, which strongly implies that Src plays a pivotal role in the functional activation of macrophages. Macrophages are involved in a variety of immune responses and in inflammatory diseases including rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer, and osteoporosis. Previous studies have suggested roles for Src in macrophage-mediated inflammatory responses; however, recently, new functions for Src have been reported, implying that Src functions in macrophage-mediated inflammatory responses that have not been described. In this paper, we discuss recent studies regarding a number of these newly defined functions of Src in macrophage-mediated inflammatory responses. Moreover, we discuss the feasibility of Src as a target for the development of new pharmaceutical drugs to treat macrophage-mediated inflammatory diseases. We provide insights into recent reports regarding new functions for Src that are related to macrophage-related inflammatory responses and the development of novel Src inhibitors with strong immunosuppressive and anti-inflammatory properties, which could be applied to various macrophage-mediated inflammatory diseases. 1. Introduction Inflammation is a complex biological response to various harmful stimuli and is accompanied by various symptoms including redness, swelling, heat, and pain. A major cause of inflammation stems from the infection of local tissue with pathogens, such as bacteria, viruses, and fungi; inflammation is the process that attracts various immune cells to the injured tissues and removes the infecting pathogens. These processes involve closely related chemical mediators, such as nitric oxide (NO), reactive oxygen species (ROS), prostaglandin E2 (PGE2), histamine, and cytokines including TNF-α and various interleukins [1]. There are two types of inflammatory responses acute inflammation and chronic inflammation. Acute inflammation is a rapid and temporary host response induced by leukocytes and plasma proteins containing antibodies in the infected or injured tissues. Chronic inflammation is persistent inflammation characterized by tissue injury and attack and has a longer recovery time. The chronic response may increase damage to the tissues and organs, resulting in the onset of diseases, such as
References
[1]
M. Del Donno, D. Bittesnich, A. Chetta, D. Olivieri, and M. T. Lopez-Vidriero, “The effect of inflammation on mucociliary clearance asthma: an overview,” Chest, vol. 118, no. 4, pp. 1142–1149, 2000.
[2]
Y. P. Chong, K. K. Ia, T. D. Mulhern, and H. C. Cheng, “Endogenous and synthetic inhibitors of the Src-family protein tyrosine kinases,” Biochimica et Biophysica Acta, vol. 1754, no. 1-2, pp. 210–220, 2005.
[3]
S. J. Corey and S. M. Anderson, “Src-related protein tyrosine kinases in hematopoiesis,” Blood, vol. 93, no. 1, pp. 1–14, 1999.
[4]
T. J. Boggon and M. J. Eck, “Structure and regulation of Src family kinases,” Oncogene, vol. 23, no. 48, pp. 7918–7927, 2004.
[5]
E. Ingley, J. R. Schneider, C. J. Payne et al., “Csk-binding protein mediates sequential enzymatic down-regulation and degradation of Lyn in erythropoietin-stimulated cells,” Journal of Biological Chemistry, vol. 281, no. 42, pp. 31920–31929, 2006.
[6]
M. D. Resh, “Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins,” Biochimica et Biophysica Acta, vol. 1451, no. 1, pp. 1–16, 1999.
[7]
E. Giannoni, M. L. Taddei, and P. Chiarugi, “Src redox regulation: again in the front line,” Free Radical Biology and Medicine, vol. 49, no. 4, pp. 516–527, 2010.
[8]
C. A. Koch, D. Anderson, M. F. Moran, C. Ellis, and T. Pawson, “SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins,” Science, vol. 252, no. 5006, pp. 668–674, 1991.
[9]
R. Roskoski, “Src protein-tyrosine kinase structure and regulation,” Biochemical and Biophysical Research Communications, vol. 324, no. 4, pp. 1155–1164, 2004.
[10]
J. C. Williams, A. Weijland, S. Gonfloni et al., “The 2.35 ？ crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions,” Journal of Molecular Biology, vol. 274, no. 5, pp. 757–775, 1997.
[11]
W. Xu, S. C. Harrison, and M. J. Eck, “Three-dimensional structure of the tyrosine kinase c-Src,” Nature, vol. 385, no. 6617, pp. 595–602, 1997.
[12]
R. Roskoski, “Src kinase regulation by phosphorylation and dephosphorylation,” Biochemical and Biophysical Research Communications, vol. 331, no. 1, pp. 1–14, 2005.
[13]
M. Okada and H. Nakagawa, “A protein tyrosine kinase involved in regulation of pp60(c-src) function,” Journal of Biological Chemistry, vol. 264, no. 35, pp. 20886–20893, 1989.
[14]
S. Zrihan-Licht, J. Lim, I. Keydar, M. X. Sliwkowski, J. E. Groopman, and H. Avraham, “Association of Csk-homologous kinase (CHK) (formerly MATK) with HER- 2/ErbB-2 in breast cancer cells,” Journal of Biological Chemistry, vol. 272, no. 3, pp. 1856–1863, 1997.
[15]
Y. P. Chong, T. D. Mulhern, H. J. Zhu et al., “A novel non-catalytic mechanism employed by the C-terminal Src-homologous kinase to inhibit Src-family kinase activity,” Journal of Biological Chemistry, vol. 279, no. 20, pp. 20752–20766, 2004.
[16]
M. Baker, J. Gamble, R. Tooze et al., “Development of T-leukaemias in CD45 tyrosine phosphatase-deficient mutant lck mice,” EMBO Journal, vol. 19, no. 17, pp. 4644–4654, 2000.
[17]
G. G. Chiang and B. M. Sefton, “Specific dephosphorylation of the lck tyrosine protein knase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase,” Journal of Biological Chemistry, vol. 276, no. 25, pp. 23173–23178, 2001.
[18]
V. A. Levin, “Basis and importance of Src as a target in cancer.,” Cancer treatment and research, vol. 119, pp. 89–119, 2004.
[19]
J. Su, M. Muranjan, and J. Sap, “Receptor protein tyrosine phosphatase α activates Src-family kinases and controls integrin-mediated responses in fibroblasts,” Current Biology, vol. 9, no. 10, pp. 505–511, 1999.
[20]
I. Zachary, “VEGF signalling: integration and multi-tasking in endothelial cell biology,” Biochemical Society Transactions, vol. 31, no. 6, pp. 1171–1177, 2003.
[21]
Z. Korade-Mirnics and S. J. Corey, “Src kinase-mediated signaling in leukocytes,” Journal of Leukocyte Biology, vol. 68, no. 5, pp. 603–613, 2000.
[22]
M. V. Barone and S. A. Courtneidge, “Myc but not Fos rescue of PDGF signalling block caused by kinase-inactive Src,” Nature, vol. 378, no. 6556, pp. 509–512, 1995.
[23]
S. A. Courtneidge, R. Dhand, D. Pilat, G. M. Twamley, M. D. Waterfield, and M. F. Roussel, “Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor,” EMBO Journal, vol. 12, no. 3, pp. 943–950, 1993.
[24]
M. E. Kehrli, J. L. Burton, B. J. Nonnecke, and E. K. Lee, “Effects of stress on leukocyte trafficking and immune responses: implications for vaccination,” Advances in Veterinary Medicine, vol. 41, no. C, pp. 61–81, 1999.
[25]
S. M. Thomas, P. Soriano, and A. Imamoto, “Specific and redundant roles of Src and Fyn in organizing the cytoskeleton,” Nature, vol. 376, no. 6537, pp. 267–271, 1995.
[26]
K. Burridge, C. E. Turner, and L. H. Romer, “Tyrosine phosphorylation of paxillin and pp125(FAK) accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly,” Journal of Cell Biology, vol. 119, no. 4, pp. 893–903, 1992.
[27]
D. D. Schlaepfer, S. K. Hanks, T. Hunter, and P. Van der Geer, “Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase,” Nature, vol. 372, no. 6508, pp. 786–791, 1994.
[28]
E. Rozengurt, “Mitogenic signaling pathways induced by G protein-coupled receptors,” Journal of Cellular Physiology, vol. 213, no. 3, pp. 589–602, 2007.
[29]
K. Zen and Y. Liu, “Role of different protein tyrosine kinases in fMLP-induced neutrophil transmigration,” Immunobiology, vol. 213, no. 1, pp. 13–23, 2008.
[30]
J. S. Gutkind, “The pathways connecting G protein-coupled receptors to the nucleus through divergent mitogen-activated protein kinase cascades,” Journal of Biological Chemistry, vol. 273, no. 4, pp. 1839–1842, 1998.
[31]
P. A. Kiener, B. M. Rankin, A. L. Burkhardt et al., “Cross-linking of Fcγ receptor I (FcγRI) and receptor II (FcγRII) on monocytic cells activates a signal transduction pathway common to both Fc receptors that involves the stimulation of p72 Syk protein tyrosine kinase,” Journal of Biological Chemistry, vol. 268, no. 32, pp. 24442–24448, 1993.
[32]
G. Sánchez-Mejorada and C. Rosales, “Signal transduction by immunoglobulin Fc receptors,” Journal of Leukocyte Biology, vol. 63, no. 5, pp. 521–533, 1998.
[33]
S. C. Silverstein, S. Greenberg, F. DiVergilio, and T. Steinberg, Fundamental Immunology, Raven, New York, NY, USA, 1989.
[34]
N. Bewarder, V. Weinrich, P. Budde et al., “In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcγRII) phosphorylation,” Molecular and Cellular Biology, vol. 16, no. 9, pp. 4735–4743, 1996.
[35]
J. B. Bolen, R. B. Rowley, C. Spana, and A. Y. Tsygankov, “The Src family of tyrosine protein kinases in hemopoietic signal transduction,” FASEB Journal, vol. 6, no. 15, pp. 3403–3409, 1992.
[36]
M. M. Huang, Z. Indik, L. F. Brass, J. A. Hoxie, A. D. Schreiber, and J. S. Brugge, “Activation of FcγRII induces tyrosine phosphorylation of multiple proteins including FcγRII,” Journal of Biological Chemistry, vol. 267, no. 8, pp. 5467–5473, 1992.
[37]
S. Hunter, L. M. Huang, Z. K. Indik, and A. D. Schreiber, “FcγRIIA-mediated phagocytosis and receptor phosphorylation in cells deficient in the protein tyrosine kinase Src,” Experimental Hematology, vol. 21, no. 11, pp. 1492–1497, 1993.
[38]
G. T. Williams, C. A. Smith, E. Spooncer, T. M. Dexter, and D. R. Taylor, “Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis,” Nature, vol. 343, no. 6253, pp. 76–79, 1990.
[39]
S. M. Anderson, P. M. Carroll, and F. D. Lee, “Abrogation of IL-3 dependent growth requires a functional v-src gene product: evidence for an autocrine growth cycle,” Oncogene, vol. 5, no. 3, pp. 317–325, 1990.
[40]
F. Dong and A. C. Larner, “Activation of Akt kinase by granulocyte colony-stimulating factor (G- CSF): evidence for the role of a tyrosine kinase activity distinct from the janus kinases,” Blood, vol. 95, no. 5, pp. 1656–1662, 2000.
[41]
T. H. Page, M. Smolinska, J. Gillespie, A. M. Urbaniak, and B. M. J. Foxwell, “Tyrosine kinases and inflammatory signalling,” Current Molecular Medicine, vol. 9, no. 1, pp. 69–85, 2009.
[42]
M. S. Lee and Y. J. Kim, “Signaling pathways downstream of pattern-recognition receptors and their cross talk,” Annual Review of Biochemistry, vol. 76, pp. 447–480, 2007.
[43]
T. Kaisho and S. Akira, “Critical roles of Toll-like receptors in host defense,” Critical Reviews in Immunology, vol. 20, no. 5, pp. 393–405, 2000.
[44]
C. Mohan and J. Zhu, “Toll-like receptor signaling pathways—therapeutic opportunities,” Mediators of Inflammation, vol. 2010, Article ID 781235, 7 pages, 2010.
[45]
L. A. J. O'Neill, “Primer: toll-like receptor signaling pathways-what do rheumatologists need to know?” Nature Clinical Practice Rheumatology, vol. 4, no. 6, pp. 319–327, 2008.
[46]
K. S. Kim, B. Y. Rhim, S. K. Eo, and K. Kim, “Cellular signaling molecules associated with peptidoglycan-induced ccl3 up-regulation,” Biomolecules and Therapeutics, vol. 19, no. 3, pp. 302–307, 2011.
[47]
C. H. Tang, C. J. Hsu, W. H. Yang, and Y. C. Fong, “Lipoteichoic acid enhances IL-6 production in human synovial fibroblasts via TLR2 receptor, PKCδ and c-Src dependent pathways,” Biochemical Pharmacology, vol. 79, no. 11, pp. 1648–1657, 2010.
[48]
H. L. Hsieh, H. H. Wang, C. Y. Wu, W. H. Tung, and C. M. Yang, “Lipoteichoic acid induces matrix metalloproteinase-9 expression via transactivation of PDGF receptors and NF-kappaB activation in rat brain astrocytes.,” Neurotoxicity Research, vol. 17, no. 4, pp. 344–359, 2010.
[49]
M. Liljeroos, R. Vuolteenaho, S. Morath, T. Hartung, M. Hallman, and M. Ojaniemi, “Bruton's tyrosine kinase together with PI 3-kinase are part of Toll-like receptor 2 multiprotein complex and mediate LTA induced Toll-like receptor 2 responses in macrophages,” Cellular Signalling, vol. 19, no. 3, pp. 625–633, 2007.
[50]
Y. J. Chang, M. S. Wu, J. T. Lin et al., “Induction of cyclooxygenase-2 overexpression in human gastric epithelial cells by Helicobacter pylori involves TLR2/TLR9 and c-Src-dependent nuclear factor-κB activation,” Molecular Pharmacology, vol. 66, no. 6, pp. 1465–1477, 2004.
[51]
R. Adamo, S. Sokol, G. Soong, M. I. Gomez, and A. Prince, “Pseudomonas aeruginosa flagella activate airway epithelial cells through asialoGM1 and toll-like receptor 2 as well as toll-like receptor 5,” American Journal of Respiratory Cell and Molecular Biology, vol. 30, no. 5, pp. 627–634, 2004.
[52]
J. Chun and A. Prince, “Ca2+ signaling in airway epithelial cells facilitates leukocyte recruitment and transepithelial migration,” Journal of Leukocyte Biology, vol. 86, no. 5, pp. 1135–1144, 2009.
[53]
M. Yamashita, S. Chattopadhyay, V. Fensterl, Y. Zhang, and G. C. Sen, “A TRIF-independent branch of TLR3 signaling,” Journal of Immunology, vol. 188, no. 6, pp. 2825–2833, 2012.
[54]
Y. J. Chen, M. Y. Hsieh, M. Y. Chang, et al., “Eps8 protein facilitates phagocytosis by increasing TLR4-MyD88 protein interaction in lipopolysaccharide-stimulated macrophages,” The Journal of Biological Chemistry, vol. 287, no. 22, pp. 18806–18819, 2012.
[55]
T. T. Nguyen, I. B. Johnsen, C. F. Knetter et al., “Differential gene expression downstream of toll-like receptors (TLRs): role of c-Src and activating transcription factor 3 (ATF3),” Journal of Biological Chemistry, vol. 285, no. 22, pp. 17011–17019, 2010.
[56]
D. Gianni, B. Bohl, S. A. Courtneidge, and G. M. Bokoch, “The involvement of the tyrosine kinase c-Src in the regulation of reactive oxygen species generation mediated by NADPH oxidase-1,” Molecular Biology of the Cell, vol. 19, no. 7, pp. 2984–2994, 2008.
[57]
H. J. Kim, S. G. Lee, I. G. Chae et al., “Antioxidant effects of fermented red ginseng extracts in streptozotocin- induced diabetic rats,” Journal of Ginseng Research, vol. 35, no. 2, pp. 129–137, 2011.
[58]
M. R. Abid, Z. Kachra, K. C. Spokes, and W. C. Aird, “NADPH oxidase activity is required for endothelial cell proliferation and migration,” FEBS Letters, vol. 486, no. 3, pp. 252–256, 2000.
[59]
S. Kim, J. Y. Kim, Z. Y. Ryoo, and S. Lee, “Over-expressed peroxiredoxin I protects against oxidative damage in mouse embryonic fibroblasts lacking peroxiredoxin II,” Biomolecules & Therapeutics, vol. 19, no. 4, pp. 451–459, 2011.
[60]
Y. A. Suh, R. S. Arnold, B. Lassegue et al., “Cell transformation by the superoxide-generating oxidase Mox1,” Nature, vol. 401, no. 6748, pp. 79–82, 1999.
[61]
A. Sadok, V. Bourgarel-Rey, F. Gattacceca, C. Penel, M. Lehmann, and H. Kovacic, “Nox1-dependent superoxide production controls colon adenocarcinoma cell migration,” Biochimica et Biophysica Acta, vol. 1783, no. 1, pp. 23–33, 2008.
[62]
H. Yang, S. E. Lee, S. I. Jeong, C. S. Park, Y. H. Jin, and Y. S. Park, “Up-regulation of heme oxygenase-1 by Korean red ginseng water extract as a cytoprotective effect in human endothelial cells,” Journal of Ginseng Research, vol. 35, no. 3, pp. 352–359, 2011.
[63]
A. K. Chowdhury, T. Watkins, N. L. Parinandi et al., “Src-mediated tyrosine phosphorylation of p47phox in hyperoxia-induced activation of NADPH oxidase and generation of reactive oxygen species in lung endothelial cells,” Journal of Biological Chemistry, vol. 280, no. 21, pp. 20700–20711, 2005.
[64]
Z. Wang, T. Rui, M. Yang, F. Valiyeva, and P. R. Kvietys, “Alveolar macrophages from septic mice promote polymorphonuclear leukocyte transendothelial migration via an endothelial cell Src kinase/NADPH oxidase pathway,” Journal of Immunology, vol. 181, no. 12, pp. 8735–8744, 2008.
[65]
H. Sumimoto, K. Hata, K. Mizuki et al., “Assembly and activation of the phagocyte NADPH oxidase: specific interaction of the N-terminal Src homology 3 domain of p47(phox) with p22(phox) is required for activation of the NADPH oxidase,” Journal of Biological Chemistry, vol. 271, no. 36, pp. 22152–22158, 1996.
[66]
H. S. Deshmukh, C. Shaver, L. M. Case et al., “Acrolein-activated matrix metalloproteinase 9 contributes to persistent mucin production,” American Journal of Respiratory Cell and Molecular Biology, vol. 38, no. 4, pp. 446–454, 2008.
[67]
W. Ning, Y. Dong, J. Sun et al., “Cigarette smoke stimulates matrix metalloproteinase-2 activity via EGR-1 in human lung fibroblasts,” American Journal of Respiratory Cell and Molecular Biology, vol. 36, no. 4, pp. 480–490, 2007.
[68]
J. Arredondo, A. I. Chernyavsky, D. L. Jolkovsky, K. E. Pinkerton, and S. A. Grando, “Receptor-mediated tobacco toxicity: acceleration of sequential expression of α5 and α7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke,” FASEB Journal, vol. 22, no. 5, pp. 1356–1368, 2008.
[69]
S. W. Ryter, H. P. Kim, K. Nakahira, B. S. Zuckerbraun, D. Morse, and A. M. K. Choi, “Protective functions of heme oxygenase-1 and carbon monoxide in the respiratory system,” Antioxidants and Redox Signaling, vol. 9, no. 12, pp. 2157–2173, 2007.
[70]
J. Cohen, “The immunopathogenesis of sepsis,” Nature, vol. 420, no. 6917, pp. 885–891, 2002.
[71]
L. B. Ware and M. A. Matthay, “The acute respiratory distress syndrome,” New England Journal of Medicine, vol. 342, no. 18, pp. 1334–1349, 2000.
[72]
P. Zhang, W. R. Summer, G. J. Bagby, and S. Nelson, “Innate immunity and pulmonary host defense,” Immunological Reviews, vol. 173, pp. 39–51, 2000.
[73]
C. Delclaux and E. Azoulay, “Inflammatory response to infectious pulmonary injury,” European Respiratory Journal, Supplement, vol. 22, no. 42, 2003.
[74]
K. S. Farley, L. F. Wang, H. M. Razavi et al., “Effects of macrophage inducible nitric oxide synthase in murine septic lung injury,” American Journal of Physiology, vol. 290, no. 6, pp. L1164–L1172, 2006.
[75]
C. Moon, H. J. Park, Y. H. Choi, E. M. Park, V. Castranova, and J. L. Kang, “Pulmonary inflammation after intraperitoneal administration of ultrafine titanium dioxide (TiO2) at rest or in lungs primed with lipopolysaccharide,” Journal of Toxicology and Environmental Health A, vol. 73, no. 5-6, pp. 396–409, 2010.
[76]
P. L. Stein, H. M. Lee, S. Rich, and P. Soriano, “pp59(fyn) mutant mice display differential signaling in thymocytes and peripheral T cells,” Cell, vol. 70, no. 5, pp. 741–750, 1992.
[77]
E. Gaudreault, C. Thompson, J. Stankova, and M. Rola-Pleszczynski, “Involvement of BLT1 endocytosis and Yes kinase activation in leukotriene B4-induced neutrophil degranulation,” Journal of Immunology, vol. 174, no. 6, pp. 3617–3625, 2005.
[78]
S. N. Malek, D. I. Dordai, J. Reim, H. Dintzis, and S. Desiderio, “Malignant transformation of early lymphoid progenitors in mice expressing an activated Blk tyrosine kinase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 13, pp. 7351–7356, 1998.
[79]
F. Chiaradonna, L. Fontana, C. Iavarone et al., “Urokinase receptor-dependent and -independent p56/59(hck) activation state is a molecular switch between myelomonocytic cell motility and adherence,” EMBO Journal, vol. 18, no. 11, pp. 3013–3023, 1999.
[80]
C. J. Fitzer-Attas, M. Lowry, M. T. Crowley et al., “Fcγ receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn,” Journal of Experimental Medicine, vol. 191, no. 4, pp. 669–681, 2000.
[81]
J. M. Dal Porto, K. Burke, and J. C. Cambier, “Regulation of BCR signal transduction in B-1 cells requires the expression of the Src family kinase Lck,” Immunity, vol. 21, no. 3, pp. 443–453, 2004.
[82]
M. L. Hibbs, D. M. Tarlinton, J. Armes et al., “Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease,” Cell, vol. 83, no. 2, pp. 301–311, 1995.
[83]
S. K. Yoo, T. W. Starnes, Q. Deng, and A. Huttenlocher, “Lyn is a redox sensor that mediates leukocyte wound attraction in vivo,” Nature, vol. 480, no. 7375, pp. 109–112, 2011.
[84]
Z. Ming, Y. Hu, J. Xiang, P. Polewski, P. J. Newman, and D. K. Newman, “Lyn and PECAM-1 function as interdependent inhibitors of platelet aggregation,” Blood, vol. 117, no. 14, pp. 3903–3906, 2011.
[85]
A. K. Somani, J. S. Bignon, G. B. Mills, K. A. Siminovitch, and D. R. Branch, “Src kinase activity is regulated by the SHP-1 protein-tyrosine phosphatase,” Journal of Biological Chemistry, vol. 272, no. 34, pp. 21113–21119, 1997.
[86]
J. D. Bjorge, A. Pang, and D. J. Fujita, “Identification of protein-tyrosine phosphatase 1B as the major tyrosine phosphatase activity capable of dephosphorylating and activating c-Src in several human breast cancer cell lines,” Journal of Biological Chemistry, vol. 275, no. 52, pp. 41439–41446, 2000.
[87]
D. A. Jones and C. W. Benjamin, “Phosphorylation of growth factor receptor binding protein-2 by pp60(c- src) tyrosine kinase,” Archives of Biochemistry and Biophysics, vol. 337, no. 2, pp. 143–148, 1997.
[88]
L. R. Stephens, K. E. Anderson, and P. T. Hawkins, “Src Family Kinases Mediate Receptor-stimulated, Phosphoinositide 3-Kinase-dependent, Tyrosine Phosphorylation of Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides-1 in Endothelial and B Cell Lines,” Journal of Biological Chemistry, vol. 276, no. 46, pp. 42767–42773, 2001.
[89]
A. Ostareck-Lederer, D. H. Ostareck, C. Cans et al., “c-Src-mediated phosphorylation of hnRNP K drives translational activation of specifically silenced mRNAs,” Molecular and Cellular Biology, vol. 22, no. 13, pp. 4535–4543, 2002.
[90]
G. S. Goldberg, D. B. Alexander, P. Pellicena, Z. Y. Zhang, H. Tsuda, and W. T. Miller, “Src Phosphorylates Cas on Tyrosine 253 to Promote Migration of Transformed Cells,” Journal of Biological Chemistry, vol. 278, no. 47, pp. 46533–46540, 2003.
[91]
B. W. Howell, T. M. Herrick, J. D. Hildebrand, Y. Zhang, and J. A. Cooper, “Dab1 tyrosine phosphorylation sites relay positional signals during mouse brain development,” Current Biology, vol. 10, no. 15, pp. 877–885, 2000.
[92]
G. Kato and S. Maeda, “Neuron-specific Cdk5 kinase is responsible for mitosis-independent phosphorylation of c-Src at Ser75 in human Y79 retinoblastoma cells,” Journal of Biochemistry, vol. 126, no. 5, pp. 957–961, 1999.
[93]
Z. Tiran, A. Peretz, B. Attali, and A. Elson, “Phosphorylation-dependent regulation of Kv2.1 Channel activity at tyrosine 124 by Src and by protein-tyrosine phosphatase ε,” Journal of Biological Chemistry, vol. 278, no. 19, pp. 17509–17514, 2003.
[94]
G. H. Renkema, K. Pulkkinen, and K. Saksela, “Cdc42/Rac1-mediated activation primes PAK2 for superactivation by tyrosine phosphorylation,” Molecular and Cellular Biology, vol. 22, no. 19, pp. 6719–6725, 2002.
[95]
Z. Zhang, G. Izaguirre, S. Y. Lin, H. Y. Lee, E. Schaefer, and B. Haimovich, “The phosphorylation of vinculin on tyrosine residues 100 and 1065, mediated by Src kinases, affects cell spreading,” Molecular Biology of the Cell, vol. 15, no. 9, pp. 4234–4247, 2004.
[96]
P. N. Garrison, A. K. Robinson, Y. Pekarsky, C. M. Croce, and L. D. Barnes, “Phosphorylation of the human Fhit tumor suppressor on tyrosine 114 in Escherichia coli and unexpected steady state kinetics of the phosphorylated forms,” Biochemistry, vol. 44, no. 16, pp. 6286–6292, 2005.
[97]
W. Seok Yang, J. Lee, T. Woong Kim, et al., “Src/NF-kappaB-targeted inhibition of LPS-induced macrophage activation and dextran sodium sulphate-induced colitis by Archidendron clypearia methanol extract,” Journal of Ethnopharmacology, vol. 142, no. 1, pp. 287–293, 2012.
[98]
Y. Yang, T. Yu, H. J. Jang, et al., “In vitro and in vivo anti-inflammatory activities of Polygonum hydropiper methanol extract,” Journal of Ethnopharmacology, vol. 139, no. 2, pp. 616–625, 2012.
[99]
T. Yu, S. Lee, W. S. Yang, et al., “The ability of an ethanol extract of Cinnamomum cassia to inhibit Src and spleen tyrosine kinase activity contributes to its anti-inflammatory action,” Journal of Ethnopharmacology, vol. 139, no. 2, pp. 566–573, 2012.
[100]
T. Yu, H. M. Ahn, T. Shen, et al., “Anti-inflammatory activity of ethanol extract derived from Phaseolus angularis beans,” Journal of Ethnopharmacology, vol. 137, no. 3, pp. 1197–1206, 2011.
[101]
T. Yu, Y. J. Lee, H. J. Jang et al., “Anti-inflammatory activity of Sorbus commixta water extract and its molecular inhibitory mechanism,” Journal of Ethnopharmacology, vol. 134, no. 2, pp. 493–500, 2011.
[102]
T. Yu, Y. J. Lee, H. M. Yang et al., “Inhibitory effect of Sanguisorba officinalis ethanol extract on NO and PGE2 production is mediated by suppression of NF-κB and AP-1 activation signaling cascade,” Journal of Ethnopharmacology, vol. 134, no. 1, pp. 11–17, 2011.
[103]
M. H. Kim, S. Y. Ryu, J. S. Choi, Y. K. Min, and S. H. Kim, “Saurolactam inhibits osteoclast differentiation and stimulates apoptosis of mature osteoclasts,” Journal of Cellular Physiology, vol. 221, no. 3, pp. 618–628, 2009.
[104]
J. Y. Kim, Y. G. Lee, M. Y. Kim et al., “Src-mediated regulation of inflammatory responses by actin polymerization,” Biochemical Pharmacology, vol. 79, no. 3, pp. 431–443, 2010.
[105]
M. C. Maa, M. Y. Chang, M. Y. Hsieh et al., “Butyrate reduced lipopolysaccharide-mediated macrophage migration by suppression of Src enhancement and focal adhesion kinase activity,” Journal of Nutritional Biochemistry, vol. 21, no. 12, pp. 1186–1192, 2010.
[106]
J. Y. Cho, D. S. Yoo, J. Lee et al., “A modulatory effect of novel kojic acid derivatives on cancer cell proliferation and macrophage activation,” Pharmazie, vol. 65, no. 4, pp. 261–266, 2010.
[107]
C. Li, Z. Yang, Z. Li et al., “Maslinic acid suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by regulating RANKL-mediated NF-κB and MAPK signaling pathways,” Journal of Bone and Mineral Research, vol. 26, no. 3, pp. 644–656, 2011.
[108]
H. S. Kim, K. S. Suh, D. Sul, B. J. Kim, S. K. Lee, and W. W. Jung, “The inhibitory effect and the molecular mechanism of glabridin on RANKL-induced osteoclastogenesis in RAW264.7 cells,” International Journal of Molecular Medicine, vol. 29, no. 2, pp. 169–177, 2012.
[109]
D. Pinkaew, N. Hutadilok-Towatana, B. B. Teng, W. Mahabusarakam, and K. Fujise, “Morelloflavone, a biflavonoid inhibitor of migration-related kinases, ameliorates atherosclerosis in mice,” American Journal of Physiology, vol. 302, no. 2, pp. 451–458, 2012.
[110]
A. R. Kim, H. S. Kim, J. M. Lee, et al., “Arctigenin suppresses receptor activator of nuclear factor kappaB ligand (RANKL)-mediated osteoclast differentiation in bone marrow-derived macrophages,” European Journal of Pharmacology, vol. 682, no. 1–3, pp. 29–36, 2012.
[111]
R. Fumimoto, E. Sakai, Y. Yamaguchi, et al., “The coffee diterpene kahweol prevents osteoclastogenesis via impairment of NFATc1 expression and blocking of Erk phosphorylation,” Journal of Pharmacological Sciences, vol. 118, no. 4, pp. 479–486, 2012.
[112]
M. P. Nelson, B. S. Christmann, J. L. Werner et al., “IL-33 and M2a alveolar macrophages promote lung defense against the atypical fungal pathogen Pneumocystis murina,” Journal of Immunology, vol. 186, no. 4, pp. 2372–2381, 2011.
[113]
H. S. Lee, C. Moon, H. W. Lee, E. M. Park, M. S. Cho, and J. L. Kang, “Src tyrosine kinases mediate activations of NF-κB and integrin signal during lipopolysaccharide-induced acute lung injury,” Journal of Immunology, vol. 179, no. 10, pp. 7001–7011, 2007.
[114]
M. K. Dahle, G. ？verland, A. E. Myhre et al., “The phosphatidylinositol 3-kinase/protein kinase B signaling pathway is activated by lipoteichoic acid and plays a role in Kupffer cell production of interleukin-6 (IL-6) and IL-10,” Infection and Immunity, vol. 72, no. 10, pp. 5704–5711, 2004.
[115]
T. R. Billiar, R. D. Curran, M. A. West, K. Hofmann, and R. L. Simmons, “Kupffer cell cytotoxicity to hepatocytes in coculture requires L-arginine,” Archives of Surgery, vol. 124, no. 12, pp. 1416–1421, 1989.
[116]
J. F. Dhainaut, N. Marin, A. Mignon, C. Vinsonneau, and C. Sprung, “Hepatic response to sepsis: interaction between coagulation and inflammatory processes,” Critical Care Medicine, vol. 29, no. 7, pp. S42–S47, 2001.
[117]
D. Jarrar, I. H. Chaudry, and P. Wang, “Organ dysfunction following hemorrhage and sepsis: mechanisms and therapeutic approaches (Review).,” International journal of molecular medicine, vol. 4, no. 6, pp. 575–583, 1999.
[118]
D. J. Koo, I. H. Chaudry, and P. Wang, “Kupffer cells are responsible for producing inflammatory cytokines and hepatocellular dysfunction during early sepsis,” Journal of Surgical Research, vol. 83, no. 2, pp. 151–157, 1999.
[119]
M. A. West, T. R. Billiar, R. D. Curran, B. J. Hyland, and R. L. Simmons, “Evidence that rat Kupffer cells stimulate and inhibit hepatocyte protein synthesis in vitro by different mechanisms,” Gastroenterology, vol. 96, no. 6, pp. 1572–1582, 1989.
[120]
T. R. Billiar and R. D. Curran, “Kupffer cell and hepatocyte interactions: a brief overview,” Journal of Parenteral and Enteral Nutrition, vol. 14, no. 5, 1990.
[121]
A. Jerin, N. Po？ar-Lukanovi？, V. Sojar, D. Stanisavljevi？, V. Paver-Er？en, and J. Osredkar, “Balance of pro- and anti-inflammatory cytokines in liver surgery,” Clinical Chemistry and Laboratory Medicine, vol. 41, no. 7, pp. 899–903, 2003.
[122]
K. Emmanuilidis, H. Weighardt, S. Maier et al., “Critical role of Kupffer cell-derived IL-10 for host defense in septic peritonitis,” Journal of Immunology, vol. 167, no. 7, pp. 3919–3927, 2001.
[123]
M. Kato, N. Ikeda, E. Matsushita, S. Kaneko, and K. Kobayashi, “Involvement of IL-10, an anti-inflammatory cytokine in murine liver injury induced by Concanavalin A,” Hepatology Research, vol. 22, no. 2, pp. 232–243, 2001.
[124]
F. D. Lowy, “Medical progress: staphylococcus aureus infections,” New England Journal of Medicine, vol. 339, no. 8, pp. 520–532, 1998.
[125]
P. J. O'Neill, A. Ayala, P. Wang et al., “Role of Kupffer cells in interleukin-6 release following trauma-hemorrhage and resuscitation.,” Shock, vol. 1, no. 1, pp. 43–47, 1994.
[126]
M. J. Richards, J. R. Edwards, D. H. Culver, and R. P. Gaynes, “Nosocomial infections in medical intensive care units in the United States,” Critical Care Medicine, vol. 27, no. 5, pp. 887–892, 1999.
[127]
S. B. Yee, P. E. Ganey, and R. A. Roth, “The role of kupffer cells and TNF-α in monocrotaline and bacterial lipopolysaccharide-induced liver injury,” Toxicological Sciences, vol. 71, no. 1, pp. 124–132, 2003.
[128]
H. Fan, G. Teti, S. Ashton et al., “Involvement of Gi proteins and Src tyrosine kinase in TNFα production induced by lipopolysaccharide, group B Streptococci and Staphylococcus aureus,” Cytokine, vol. 22, no. 5, pp. 126–133, 2003.
[129]
R. Zheng, G. Pan, B. M. Thobe et al., “MyD88 and Src are differentially regulated in Kupffer cells of males and proestrus females following hypoxia,” Molecular Medicine, vol. 12, no. 4–6, pp. 65–73, 2006.
[130]
B. M. Thobe, M. Frink, M. A. Choudhry, M. G. Schwacha, K. I. Bland, and I. H. Chaudry, “Src family kinases regulate p38 MAPK-mediated IL-6 production in Kupffer cells following hypoxia,” American Journal of Physiology, vol. 291, no. 3, pp. C476–C482, 2006.
[131]
J. R. Sunohara, N. D. Ridgway, H. W. Cook, and D. M. Byers, “Regulation of MARCKS and MARCKS-related protein expression in BV-2 microglial cells in response to lipopolysaccharide,” Journal of Neurochemistry, vol. 78, no. 3, pp. 664–672, 2001.
[132]
G. W. Kreutzberg, “Microglia: a sensor for pathological events in the CNS,” Trends in Neurosciences, vol. 19, no. 8, pp. 312–318, 1996.
[133]
F. González-Scarano and G. Baltuch, “Microglia as mediators of inflammatory and degenerative diseases,” Annual Review of Neuroscience, vol. 22, pp. 219–240, 1999.
[134]
A. L. DeFranco, M. T. Crowley, A. Finn, J. Hambleton, and S. L. Weinstein, “The role of tyrosine kinases and map kinases in LPS-induced signaling.,” Progress in Clinical and Biological Research, vol. 397, pp. 119–136, 1998.
[135]
F. Meng and C. A. Lowell, “Lipopolysaccharide (LPS)-induced macrophage activation and signal transduction in the absence of Src-family kinases Hck, Fgr, and Lyn,” Journal of Experimental Medicine, vol. 185, no. 9, pp. 1661–1670, 1997.
[136]
J. Tan, T. Town, and M. Mullan, “CD45 inhibits CD40L-induced microglial activation via negative regulation of the Src/p44/42 MAPK pathway,” Journal of Biological Chemistry, vol. 275, no. 47, pp. 37224–37231, 2000.
[137]
J. Tan, T. Town, M. Saxe, D. Paris, Y. Wu, and M. Mullan, “Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-α production that is opposed by TGF-β1 and IL-10,” Journal of Immunology, vol. 163, no. 12, pp. 6614–6621, 1999.
[138]
M. Chellaiah, N. Kizer, M. Silva, U. Alvarez, D. Kwiatkowski, and K. A. Hruska, “Gelsolin deficiency blocks podosome assembly and produces increased bone mass and strength,” Journal of Cell Biology, vol. 148, no. 4, pp. 665–678, 2000.
[139]
R. Felix, W. Hofstetter, and M. G. Cecchini, “Recent developments in the understanding of the pathophysiology of osteopetrosis,” European Journal of Endocrinology, vol. 134, no. 2, pp. 143–156, 1996.
[140]
T. Miyazaki, S. Tanaka, A. Sanjay, and R. Baron, “The role of c-Src kinase in the regulation of osteoclast function,” Modern Rheumatology, vol. 16, no. 2, pp. 68–74, 2006.
[141]
K. B. Kaplan, J. R. Swedlow, D. O. Morgan, and H. E. Varmus, “c-Src enhances the spreading of src-/- fibroblasts on fibronectin by a kinase-independent mechanism,” Genes and Development, vol. 9, no. 12, pp. 1505–1517, 1995.
[142]
F. Meng and C. A. Lowell, “A β1 integrin signaling pathway involving Src-family kinases, Cbl and PI-3 kinase is required for macrophage spreading and migration,” EMBO Journal, vol. 17, no. 15, pp. 4391–4403, 1998.
[143]
D. P. Felsenfeld, P. L. Schwartzberg, A. Venegas, R. Tse, and M. P. Sheetz, “Selective regulation of integrin-cytoskeleton interactions by the tyrosine kinase Src,” Nature Cell Biology, vol. 1, no. 4, pp. 200–206, 1999.
[144]
T. Misteli, “The concept of self-organization in cellular architecture,” Journal of Cell Biology, vol. 155, no. 2, pp. 181–185, 2001.
[145]
T. Miyazaki, H. Takayanagi, M. Isshiki et al., “In vitro and in vivo suppression of osteoclast function by adenovirus vector-induced csk gene,” Journal of Bone and Mineral Research, vol. 15, no. 1, pp. 41–51, 2000.
[146]
P. L. Schwartzberg, L. Xing, O. Hoffmann et al., “Rescue of osteoclast function by transgenic expression of kinase- deficient Src in src-/- mutant mice,” Genes and Development, vol. 11, no. 21, pp. 2835–2844, 1997.
[147]
S. F. Doisneau-Sixou, P. Cestac, S. Chouini et al., “Contrasting effects of prenyltransferase inhibitors on estrogen-dependent cell cycle progression and estrogen receptor-mediated transcriptional activity in MCF-7 cells,” Endocrinology, vol. 144, no. 3, pp. 989–998, 2003.
[148]
W. G. Kim, C. J. Guigon, L. Fozzatti, et al., “SKI-606, an Src inhibitor, reduces tumor growth, invasion, and distant metastasis in a mouse model of thyroid cancer,” Clinical Cancer Research, vol. 18, no. 5, pp. 1281–1290, 2012.
[149]
F. M. Johnson, B. Saigal, M. Talpaz, and N. J. Donato, “Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung cancer cells,” Clinical Cancer Research, vol. 11, no. 19, pp. 6924–6932, 2005.
[150]
Y. M. Chang, L. Bai, S. Liu, J. C. Yang, H. J. Kung, and C. P. Evans, “Src family kinase oncogenic potential and pathways in prostate cancer as revealed by AZD0530,” Oncogene, vol. 27, no. 49, pp. 6365–6375, 2008.
[151]
G. Martiny-Baron, P. Holzer, E. Billy et al., “The small molecule specific EphB4 kinase inhibitor NVP-BHG712 inhibits VEGF driven angiogenesis,” Angiogenesis, vol. 13, no. 3, pp. 259–267, 2010.
[152]
A. Fallah-Tafti, A. Foroumadi, R. Tiwari, et al., “Thiazolyl N-benzyl-substituted acetamide derivatives: synthesis, Src kinase inhibitory and anticancer activities,” European Journal of Medicinal Chemistry, vol. 46, no. 10, pp. 4853–4858, 2011.
[153]
Y. J. Kim, E. H. Kim, and K. B. Hahm, “Oxidative stress in inflammation-based gastrointestinal tract diseases: challenges and opportunities,” Journal of Gastroenterology and Hepatology, vol. 27, no. 6, pp. 1004–1010, 2012.
[154]
H. Zhu and Y.R. Li, “Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence,” Experimental Biology and Medicine, vol. 237, no. 5, pp. 474–480, 2012.
[155]
S. Tavakoli and R. Asmis, “Reactive oxygen species and thiol redox signaling in the macrophage biology of atherosclerosis,” Antioxidants & Redox Signaling, vol. 17, no. 12, pp. 1785–1795, 2012.
[156]
M.J. Surace and M.L. Block, “Targeting microglia-mediated neurotoxicity: the potential of NOX2 inhibitors,” Cellular and Molecular Life Sciences, vol. 69, no. 14, pp. 2409–2427, 2012.
[157]
I. T. Lee and C. M. Yang, “Role of NADPH oxidase/ROS in pro-inflammatory mediators-induced airway and pulmonary diseases,” Biochemical Pharmacology, vol. 84, no. 5, pp. 581–590, 2012.
[158]
Y. M. Go and D. P. Jones, “Cysteine/cystine redox signaling in cardiovascular disease,” Free Radical Biology and Medicine, vol. 50, no. 4, pp. 495–509, 2011.
[159]
T. Senga, K. Miyazaki, K. Machida et al., “Clustered cysteine residues in the kinase domain of v-Src: critical role for protein stability, cell transformation and sensitivity to herbimycin A,” Oncogene, vol. 19, no. 2, pp. 273–279, 2000.
[160]
T. Senga, H. Hasegawa, M. Tanaka, M. A. Rahman, S. Ito, and M. Hamaguchi, “The cysteine-cluster motif of c-Src: its role for the heavy metal-mediated activation of kinase,” Cancer Science, vol. 29, no. 3, pp. 571–575, 2008.
[161]
J. M. Lluis, F. Buricchi, P. Chiarugi, A. Morales, and J. C. Fernandez-Checa, “Dual role of mitochondrial reactive oxygen species in hypoxia signaling: activation of nuclear factor-KB via c-SRC- and oxidant-dependent cell death,” Cancer Research, vol. 67, no. 15, pp. 7368–7377, 2007.
[162]
P. Chiarugi, “Src redox regulation: there is more than meets the eye,” Molecules and Cells, vol. 26, no. 4, pp. 329–337, 2008.
[163]
D. J. Kemble and G. Sun, “Direct and specific inactivation of protein tyrosine kinases in the Src and FGFR families by reversible cysteine oxidation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 13, pp. 5070–5075, 2009.
