Adaptor proteins in protein kinase C-mediated signal transduction.
Spatial and temporal organization of signal transduction is essential in determining the speed and precision by which signaling events occur. Adaptor proteins are key to organizing signaling enzymes near their select substrates and away from others in order to optimize precision and speed of response. Here, we describe the role of adaptor proteins in determining the specific function of individual protein kinase C (PKC) isozymes. These isozyme-selective proteins were called collectively RACKs (receptors for activated C-kinase). The role of RACKs in PKC-mediated signaling was determined using isozyme-specific inhibitors and activators of the binding of each isozyme to its respective RACK. In addition to anchoring activated PKC isozymes, RACKs anchor other signaling enzymes. RACK1, the anchoring protein for activated betaIIPKC, binds for example, Src tyrosine kinase, integrin, and phosphodiesterase. RACK2, the epsilonPKC-specific RACK, is a coated-vesicle protein and thus is involved in vesicular release and cell-cell communication. Therefore, RACKs are not only adaptors for PKC, but also serve as adaptor proteins for several other signaling enzymes. Because at least some of the proteins that bind to RACKs, including PKC itself, regulate cell growth, modulating their interactions with RACKs may help elucidate signaling pathways leading to carcinogenesis and could result in the identification of novel therapeutic targets.
Schechtman
D
D
Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305-5174, USA.
Mochly-Rosen
D
D
D000818:Animals; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000517:prevention & control; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction
D007527:Isoenzymes; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010727:Phosphoric Diester Hydrolases