c-Yes response to growth factor activation

Transmembrane receptors link the extracellular environment to the internal control elements of the cell. This signaling influences cell division, differentiation, survival, motility, adhesion, spreading and vesicular transport. Central to this signaling is the Src family of nonreceptor tyrosine kinases. The most studied kinase of this nine member family, c-Src, shares a similar structure, as well as a similar expression pattern to that of another Src family protein, c-Yes. Despite high conservation in sequence, molecular studies demonstrate that the functional domains of these kinases can contribute to specificity in signaling. At the cellular level, analysis of tight junction formation also serves as a model to differentiate c-Yes and c-Src signaling. Results suggest that c-Yes promotes formation of the tight junction by phosphorylating occludin, while c-Src signaling downregulates occludin formation in a Raf-1 dependent manner. In addition, pp62(c-Yes) knockout mice exhibit a specific physiological function phenotype that is distinct from c-src -/- mice. In these studies, c-yes -/- mice exhibit decreased transcytosis of pIgA from the blood to the bile, while c-src -/- mice exhibit deficits in osteoclasts function and bone resorption. Of particular interest in this review are receptor signals that specifically influence the actions of c-Yes. Growth factors that influence many Src family proteins include the PDGF-R, CSF-1 receptor and others. Since these receptors interact with various Src-family kinases, it is predicted that specific signaling is generated by differential recruitment to the cell membrane and/or differentiated interactions with substrates and binding partners. This review provides an overview of c-Yes interactions with specific receptor signaling pathways and how this interaction potentially influences the known physiological roles of c-Yes.