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ANNUAL REVIEWS
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PROTEIN SERINE/THREONINE KINA.sES Arthur M. Edelman Department of Phannacology and Therapeutics, State University of New York at Buffalo, Buffalo, New York 14214
Donald K. Blumenthal Department of Biochemistry, University of Texas Health Center at Tyler, Tyler, Texas 75710
Edwin G. Krebs Howard Hughes Medical Institute, University of Washington, Seattle, Washington
98195
CONTENTS PERSPEC TIVES AND S UMMAR y . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
568
CYCLIC A MP -D EP END EN T PROTEIN KINASES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
568
CYCLIC G MP -D EP ENDENT PROTEIN KINASE. . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .
572
PHOSPH OR YLAS E KINAS E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
574
MY OSIN LIGH T CHAIN KINAS ES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
577
OTHER C ALCI UM (CALM OD ULIN )-DEPENDENT PROTEIN KINAS ES . . . . . . . . . . . . .
580
PROTEIN K INASE C . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .
582
H EM E-R EG ULA TED PR OTEIN KINAS E . . . . . . . . . . . . . . . . . . . . . . . . ... .. . . . . . . . . . . . . . . .. . . . . . . . . .
584
D OUBL E-S TRAND ED RNA-D EP END EN T PR OTEIN KINASE . . . . . . . . . . . . . . . . . . . . . . . . . .
586
PYRUVATE D EHYDR OGENAS E KINAS E.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
587
BRANCHED·CHAIN
K ETOACID D EHYDROGENAS E KINAS E . . . . . . . . . . . . . . . . . . . . .
589
CAS EIN KINASES I AND II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
590
RHOD OPSIN KINASE AND J3-ADR EN ERGIC REC EPTOR KINAS ES . . . . . . . . . . . . . . . . .
593
HYDR OXY METHYLGLUTARYL-CoA RED UC TAS E KINAS E
594
a
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EDELMAN, BLUMENTHAL & KREBS
Annu. Rev. Biochem. 1987.56:567-613. Downloaded from www.annualreviews.org Access provided by State University of New York - Buffalo on 03/03/15. For personal use only.
GROWTH·ASSOCIATED HISTONE HI KINAS E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
595
GLYCOGEN SYNTHASE KINASE 3 (FA) . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
595
HORMONE·STIMULATED RIBOSOMAL PROTEIN S6 KINASE . . . . . . . . . . . . .. . . . . . . . . .
596
ISOCITRATE DEHYDROGENASE KINASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
597
THYLAKOID MEMBRANE KINASE(S) . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
598
OTHER PROTEIN SERINE/THREONINE KINASES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
599
PERSPECTIVES AND SUMMARY Phosphorylation and dephosphorylation of proteins catalyzed by protein kinases and protein phosphatases are recognized as major processes for regulating cellular functions. First implicated more than 30 years ago as a means of regulating glycogen phosphorylase activity, protein phosphorylation is now known to affect a vast array of other proteins. Protein phosphorylation is particularly prominent for the role that it serves in signal transduction. Signals impinging on cells have their effects amplified and disseminated by a network of protein phosphorylation-dephosphorylation reactions, the com plexity of which we are only beginning to appreciate (reviewed in 1). The protein kinases and the protein phosphatases are both subject to control. The present review, however, is limited to the protein kinases that catalyze the phosphorylation of serine and threonine residues in proteins (for a review of protein tyrosine kinases, see 2). Primary emphasis is given to the physico chemical properties of the kinases, to the specific reactions that they catalyze, and to the molecular mechanisms by which they are regulated. Of necessity, the physiological aspects of the processes in which the individual kinases are involved are discussed only briefly. In addition, because of space limitations, the important topic of sequence homology between protein kinases is not treated (reviewed in 2).
CYCLIC AMP-DEPENDENT PROTEIN KINASES In most eukaryotes cyclic AMP (cAMP) is thought to act by binding to the regulatory (R) subunit of the cAMP-dependent protein kinase (cAK). This results in the phosphorylation of specific target proteins by the catalytic (C) subunit of the enzyme. The structure and function of cAK have recently been reviewed (3-6). cAK has a phylogenetic distribution that extends from mam mals to yeast (reviewed in 3, 7), but there is no compelling evidence for the existence of a cAK in prokaryotes (7), and in higher plants, cAl
