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Sci. STKE, 15 July 2003 REVIEWSSH2 and PTB Domains in Tyrosine Kinase SignalingJoseph Schlessinger1* and Mark A. Lemmon2
1Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA. Abstract: Intracellular signaling pathways that involve protein tyrosine kinases (PTKs) are critical for the control of most cellular processes. Dysfunctions in PTKs, or in the signaling pathways that they regulate, result in a variety of diseases such as cancer, diabetes, immune deficiency, and many others. SH2 (Src homology region 2) and PTB (phosphotyrosine-binding) domains are small protein modules that mediate protein-protein interactions involved in many signal transduction pathways. Both domains were initially identified as modules that recognize phosphorylated tyrosines in receptor tyrosine kinases and other signaling proteins. Subsequent studies have shown that, while binding of SH2 domains to their target proteins is strictly regulated by tyrosine phosphorylation, most PTB domains actually bind to their (nonphosphorylated) targets constitutively. The functions of SH2 and PTB domains include targeting of their host proteins to different cellular compartments, assembly of key components of signaling pathways in response to extracellular signals, and the control of autoinhibition, activation and dimerization of their host proteins. The information flow from the cell surface to different cellular compartments to regulate the cell cycle, cell shape and movement, cell proliferation, differentiation and cell survival are all controlled in part by SH2 and PTB domains that can recognize phosphotyrosine or particular amino acid sequence motifs in a wide variety of target molecules. *Corresponding author. Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, SHM B-204, New Haven, CT 06520, USA. Telephone, (203) 785-7395; e-mail, joseph.schlessinger{at}yale.edu
Citation: J. Schlessinger, M. A. Lemmon, SH2 and PTB Domains in Tyrosine Kinase Signaling. Sci. STKE 2003, re12 (2003). The editors suggest the following Related Resources on Science sites:In Science Signaling
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