Adaptor proteins in protein kinase C-mediated signal transduction

Spatial and temporal organization of signal transduction is essential in de termining the speed and precision by which signaling events occur. Adaptor proteins are key to organizing signaling enzymes near their select substrat es and away from others in order to optimize precision and speed of respons e. Here, we describe the role of adaptor proteins in determining the specif ic function of individual protein kinase C (PKC) isozymes. These isozyme-se lective proteins were called collectively RACKs (receptors for activated C- kinase). The role of RACKs in PKC-mediated signaling was determined using i sozyme-specific inhibitors and activators of the binding of each isozyme to its respective RACK. In addition to anchoring activated PKC isozymes, RACK s anchor other signaling enzymes. RACK1, the anchoring protein for activate d beta IIPKC, binds for example, Src tyrosine kinase, integrin, and phospho diesterase. RACK2, the epsilon PKC-specific RACK, is a coated-vesicle prote in and thus is involved in vesicular release and cell-cell communication. T herefore, RACKs are not only adaptors for PKC, but also serve as adaptor pr oteins for several other signaling enzymes. Because at least some of the pr oteins that bind to RACKs, including PKC itself, regulate cell growth, modu lating their interactions with RACKs may help elucidate signaling pathways leading to carcinogenesis and could result in the identification of novel t herapeutic targets.