%0 Journal Article
%T The STATs in cell stress-type responses
%A Andrew C Dudley
%A David Thomas
%A James Best
%A Alicia Jenkins
%J Cell Communication and Signaling
%D 2004
%I BioMed Central
%R 10.1186/1478-811x-2-8
%X In multicellular organisms, every cell comprising every tissue, organ, or organ system constantly strives to maintain homeostasis in the face of destabilizing influences. Whether it is external stimuli such as toxic chemical exposure or changes in oxygen tension, or natural alterations in pH or osmolarity due to normal cellular metabolism, each cell in the body is equipped with the molecular machinery required to sense these environmental changes and respond to them. Because these stressful stimuli can impinge on normal cellular functioning, discrete cellular sensing mechanisms have evolved to maintain homeostasis. For example, ATP depletion caused by hypoxia activates AMPK which phosphorylates multiple downstream targets to switch the cell from a mainly anabolic to catabolic state [1]. Similarly, activation of SAPK/JNK by stressors such as ultraviolet (UV) light results in activation of well-defined molecular targets [reviewed in [2]].One interesting question is how do cells translate diverse stressful stimuli into activation of specific molecular pathways? Cellular signaling from membrane to nucleus is typically accomplished through ligand/receptor activation of intracellular second messengers. In many cases these second messengers are kinases which phosphorylate substrates leading to a cascade by which successive macromolecules are triggered. Ultimately, a terminal transcription factor is activated which then translocates to the nucleus to activate specific target genes. This type of cellular signaling has been well-characterized following receptor activation by polypeptide ligands, but some forms of cellular stress such as hypoxia cause activation of specific molecular pathways in the apparent absence of ligand to receptor stimulation. Therefore, there must be alternative routes for direct activation of target genes that circumvents the canonical ligand/receptor/second messenger cascade. One such pathway that may transmit signals to the nucleus by this alternati
%U http://www.biosignaling.com/content/2/1/8