Multiple pathways control protein kinase C phosphorylation

Autor: Wolfgang H. Ziegler, Davey B. Parekh, Peter J. Parker
Rok vydání: 2000
Předmět:
Zdroj: The EMBO Journal. 19:496-503
ISSN: 1460-2075
0261-4189
DOI: 10.1093/emboj/19.4.496
Popis: The protein kinase C (PKC) family of signal transducers are characterized by a dependence upon lipids for activity. Specifically, the classical (cPKCα, β and γ) and novel (nPKCδ, ϵ, η and θ) PKC isotypes display a physiological requirement for diacylglycerol for activity. This property of PKC has defined a now well established signalling pathway operating through receptors to phosphatidylinositol‐specific phospholipase C and hence via diacylglycerol (DAG) [and inositol (1,4,5) trisphosphate Ins(1,4,5)P3/Ca2+] to PKC (Figure 1). The operation of this pathway has been described in many cell types, and numerous reviews have covered this signalling paradigm (see Nishizuka, 1986; Hug et al ., 1993; Dekker and Parker, 1994; Jaken, 1996). Figure 1. The classical pathway of PKC activation. The scheme illustrates the production of the immediate precursor lipid PtdIns(4,5)P2 from its parent lipid PtdIns. Various agonists are linked to the phospholipases (PtdIns‐PLC) that can cleave PtdIns(4,5)P2 to diacylglycerol (DAG) and the calcium mobilizer Ins(1,4,5)P3. Calcium can affect the cPKC class by promoting membrane recruitment, but the key allosteric activator at the membrane for both cPKC and nPKC isotypes is DAG. More recently, attention has been drawn to the phosphorylation of PKC itself. Intriguingly, what was once considered a purely effector‐driven transducer turns out to possess a complex amplitude control. The elucidation of this phosphorylation control in the cPKC isotypes has formed the basis for understanding the behaviour of the immediate family, with implications for other related AGC kinases (see Hanks and Hunter, 1995; further information is available at the Protein Kinase Resource: http://www.sdsc.edu/Kinases). The further characterization of the kinases that act upon the nPKCs provides evidence of three distinct input pathways converging upon PKC. Thus, PKC serves as an elegant example of the manner in which multiple signals are integrated …
Databáze: OpenAIRE
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