SRC HOMOLOGY-2 DOMAINS - STRUCTURE, MECHANISMS, AND DRUG DISCOVERY

Src homology-2 (SH2) domains and their associated catalytic or noncata lytic proteins constitute critical signal transduction targets for dru g discovery. Such SH2 proteins are found in the regulation of a number of cellular processes, including growth, mitogenesis, motility, metab olism, immune response, and gene transcription. From the relationship of tyrosine phosphorylation and intracellular regulation by protein-ty rosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs), the dy namic and reversible binding interactions of SH2 domain containing pro teins with their cognate phosphotyrosine (pTyr) containing proteins pr ovide a third dimensionality to the orchestration of signal transducti on pathways that exist as a result of pTyr formation, degradation, and molecular recognition events. This review highlights several key rese arch achievements impacting our current understanding of SH2 structure , mechanisms, and drug discovery that underlie the role(s) of SH2 doma ins in signal transduction processes, cellular functions, and disease states. (C) 1998 John Wiley & Sons, Inc.