Tandem SH2 binding sites mediate the RasGAP-RhoGAP interaction: a conformational mechanism for SH3 domain regulation

摘要: Many cellular signaling proteins contain SH3 (Src homology 3) domains that mediate protein interactions via specific proline-containing peptides. Unlike SH2 domains, whose with tyrosine-containing peptides are promoted by phosphorylation of the binding site, regulatory mechanism for is unclear. p120 RasGAP (GTPase-activating protein), which contains an domain flanked two forms abundant SH2-mediated complex p190 RhoGAP in cells expressing activated tyrosine kinases. We have identified closely linked bind simultaneously to upon phosphorylation. This interaction expected bring into close proximity. Consequently, undergoes a conformational change results 100-fold increase accessibility target surface its domain. These indicate tandem arrangement and found variety can provide regulating SH3-dependent through In addition, it appears role promote additional