%0 Journal Article
%T Cell adhesion and signaling on the fibronectin 1st type III repeat; requisite roles for cell surface proteoglycans and integrins
%A Kwesi O Mercurius
%A Alex O Morla
%J BMC Cell Biology
%D 2001
%I BioMed Central
%R 10.1186/1471-2121-2-18
%X Cells are able to adhere to and spread on III1-C coated on a dish. Both ¦Â1 integrins and cell surface heparan sulfate proteoglycans serve as receptors for III1-C. For example, cell attachment to III1-C is partially inhibited by agents that block ¦Â1 integrins or by heparin. Complete inhibition of cell attachment is seen only when integrin blocking agents are combined with heparin. Affinity chromatography revealed the binding of proteins that likely represent the integrin ¦Â1 and ¦Á5 submits to a III1-C column. Cell adhesion to III1-C results in robust ERK1/2 activation that is blocked by integrin-blocking agents. In addition, cell adhesion to III1-C and ERK1/2 activation by III1-C are both inhibited by heparan sulfate but not by chondroitin sulfate. Moreover, heparitinase treatment, but not chondroitinase treatment of RASMCs results in reduced cell adhesion and ERK1/2 activation. Affinity chromatography experiments demonstrated that 35SO4-labeled cell surface heparan sulfate proteoglycans bound specifically to III1-C.The results suggest that the 1st type III repeat of fibronectin contains a previously unrecognized cell adhesion domain that stimulates robust ERK1/2 activation in RASMCs. Cells interact with this domain through cell surface heparan sulfate proteoglycans and integrins, and both classes of receptors are required for optimal cell adhesion and ERK1/2 activation.Fibronectin can control many aspects of cell behavior, including cell growth, migration and differentiation [1]. Fibronectin exists in the blood as a dimer, but in tissues it is in the form of an insoluble fibrillar matrix. The fibrillar form of fibronectin is thought to be the most relevant form in vivo because this is the form with which most cells interact [1]. Various lines of evidence suggest that the fibrillar matrix form of fibronectin exerts effects on cells that are not duplicated by the dimeric form of fibronectin. For example, high concentrations of dimeric fibronectin enhance cell migration
%U http://www.biomedcentral.com/1471-2121/2/18