Src Protein Tyrosine Kinases in Stress Responses

A role of Src family protein Tyrosine kinases (SFK) as mediators of receptor-ligand initiated responses is well established. Well documented, but less well understood is the role of SFK in cellular reaction to stresses. Evidence from the wide variety of experimental systems indicates that SFK mediate responses to all major classes of stress, including oxidation, DNA damage, mechanical impacts, and protein denaturing. SFK may be activated by stresses directly or via regulatory circuits whose identity is not yet fully understood. Depending on the cell type and the nature of activating stimulus, SFK may activate known downstream signaling cascades leading to cell survival, proliferation, cytoskeletal rearrangement, and apoptosis; the identity of these cascades is discussed. As in the case of receptor-initiated signaling, roles of individual SFK in various stress response may be redundant or non-redundant. Although signals generated by different stresses are generally transduced via distinct SFK pathways, these pathways may overlap or exhibit crosstalk. In some cell types stress-induced activation of SFK promotes survival and inhibits apoptosis, whereas the opposite may be true for other cell types. Stress responses constitute a new and rapidly developing area of SFK-mediated signaling.