The SH2 and SH3 adapter Nck: a two-gene family and a linker between tyrosine kinases and multiple signaling networks.
SH2 and SH3 adapter proteins connect cell surface tyrosine kinases to intracellular signaling networks. For instance, the SH3-SH2-SH3 adapter Grb2 links receptor tyrosine kinases to the Ras pathway. Nck, composed of three SH3 domains and one SH2 domain, represents a two-gene (alpha and beta) family in mammals. Nckalpha and Nckbeta are expressed in the same cells and appear to have distinct signaling specificity. Studies show that Nck plays a role in cell mitogenesis and morphogenesis. The former uses Ras-dependent and Ras-independent pathways. The latter appears to coordinate with the Cdc42/Rac>PAK1/WASp>actin cytoskeleton pathway. Understanding the specificity of Nckalpha and Nckbeta signal transduction will provide answers for the previously often conflicting observations.
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The Department of Medicine and the Norris Cancer Center, The University of Southern California Medical School, Los Angeles 90033, USA. wli@hsc.usc.edu
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D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008934:Mitogens / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D018909:src Homology Domains
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D008934:Mitogens; C078332:Nck protein; D015513:Oncogene Proteins; D011505:Protein-Tyrosine Kinases