整合素信号通路

Integrin_Pathway

Integrin_Pathway：Signaling pathways initiated by integrins at focal contacts.The 4 major signaling pathways activated by integrin engagement in adhesion complexes are shown. The key element in all these pathways is FAK which becomes activated through autophosphorylation at Y397 and thereby allow binding of Src and Fyn for further phosphorylation and full activation. Phosphorylation of FAK at specific sites dictates its subsequent interactions with other proteins (i.e. Grb2, p130Cas, PI3K, Graf) which in turn elicit a cascade of events that lead to Cell proliferation, migration or survival. FAK can also be activated by cell surface receptors for growth factors, hormones and chemokines. Plain lines, direct activation or inhibition; dashed line, indirect functional interaction; red lines, FAK-mediated events mediated by specific phosphorylation events.

Signaling from integrins and growth factor receptors :Signal transduction cascades initiated by growth factors and extracellular matrix-integrin interactions regulate cell adhesion and migration, cell growth and differentiation, and cancer cell growth and metastasis. Ongoing efforts focus on the role of focal adhesion kinase (FAK) in mediating signals from the extracellular matrix through integrin receptors. FAK and its interacting partners play a central role in propagating signals that regulate cell motility. Using “real time” imaging models coupled with biochemical analysis of adhesion signaling pathways, we are studying the role of FAK and adhesion signaling pathways in important and interesting cellular processes, including development, vascular function and cancer. A second area focuses on the novel actin binding protein, Cortactin. Cortactin regulates actin-dependent mechanisms important for membrane ruffling, endocytosis and cell motility. Cortactin binds to and regulates the Arp2/3 complex, a multi-protein complex that regulates filopodia and lamellipodia formation by promoting “branched actin polymerization”. Cortactin also binds to cell surface receptor complexes, targeting these complexes to sites of dynamic actin rearrangement. Finally, we are developing novel approaches to both define and eventually exploit, inhibitors of adhesion signaling as potential therapeutic drugs for prostate cancer metastasis.