Joseph Schlessinger
Yale University
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Secondary Section: 21, Biochemistry Membership Type:
Member
(elected 2000)
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Research Interests
In the last 25 years, I have been investigating the intracellular signaling pathways that are regulated by polypeptide growth factors. Growth factors mediate their biological responses by binding to and activating cell surface receptors designated receptor tyrosine kinases (RTK). RTKs play an important role in the control of the cell cycle, cell migration, and metabolism, as well as cell proliferation and differentiation. It has been shown that mutations or dysfunctions in the action of RTKs can cause severe diseases such as cancer, diabetes, and many developmental disorders. Through detailed biochemical and structural studies, my laboratory has established the mechanism of action of these receptors and how they transmit their intracellular signals. Receptor activation results in recruitment of signaling proteins via specific protein modules that direct protein:protein interactions such as Src homology 2 (SH2) or phosphotyrosine binding (PTB) domains. Each activated receptor functions as a platform for the assembly of a particular repertoire of signaling proteins. The enzymatic activities and cellular localizations of signaling proteins are regulated by their SH2, SH3, PTB, PH, and other protein modules. These proteins coordinate and link between intracellular signaling pathways that were activated by RTKs.
