MOLECULAR-CLONING AND CHARACTERIZATION OF PROTEIN-KINASE-D - A TARGET FOR DIACYLGLYCEROL AND PHORBOL ESTERS WITH A DISTINCTIVE CATALYTIC DOMAIN

被引:368
作者
VALVERDE, AM [1 ]
SINNETTSMITH, J [1 ]
VANLINT, J [1 ]
ROZENGURT, E [1 ]
机构
[1] IMPERIAL CANC RES FUND, LONDON WC2A 3PX, ENGLAND
关键词
SIGNAL TRANSDUCTION; BACTERIAL EXPRESSION; PHORBOL ESTER RECEPTOR; KINASE DOMAIN;
D O I
10.1073/pnas.91.18.8572
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A serine/threonine protein kinase that binds phorbol esters and diacylglycerol (named protein kinase D, PKD) has been identified. PKD contains membrane localization signals and a cysteine-rich repeat sequence homologous to that seen in the regulatory domain of protein kinase C (PKC). A bacterially expressed N-terminal domain of PKD exhibited high-affinity phorbol ester binding activity (K-d = 35 nM). The diacylglycerol analog 1-oleoyl-2-acetylglycerol inhibited phorbol ester binding in a dose-dependent manner. The catalytic domain of PKD contains all characteristic sequence motifs of serine protein kinases but shows only a low degree of sequence similarity to PKCs. The highest identity is with the catalytic domain of myosin light-chain kinase from Dictyostelium (41%). The bacterially expressed catalytic domain of PKD efficiently phosphorylated the exogenous peptide substrate syntide 2 in serine but did not catalyze significant phosphorylation of a variety of other substrates used by PKCs and other major second messenger regulated kinases. PKD may be an unusual component in the transduction of diacylglycerol and phorbol ester signals.
引用
收藏
页码:8572 / 8576
页数:5
相关论文
共 29 条
[11]   PROTEIN-KINASE-C ISOENZYMES - DIVERGENCE IN SIGNAL TRANSDUCTION [J].
HUG, H ;
SARRE, TF .
BIOCHEMICAL JOURNAL, 1993, 291 :329-343
[12]  
JOHANNES FJ, 1994, J BIOL CHEM, V269, P6140
[13]   AN ANALYSIS OF VERTEBRATE MESSENGER-RNA SEQUENCES - INTIMATIONS OF TRANSLATIONAL CONTROL [J].
KOZAK, M .
JOURNAL OF CELL BIOLOGY, 1991, 115 (04) :887-903
[14]   CALMODULIN-DEPENDENT PROTEIN KINASE-II MEDIATES INACTIVATION OF MPF AND CSF UPON FERTILIZATION OF XENOPUS EGGS [J].
LORCA, T ;
CRUZALEGUI, FH ;
FESQUET, D ;
CAVADORE, JC ;
MERY, J ;
MEANS, A ;
DOREE, M .
NATURE, 1993, 366 (6452) :270-273
[15]   INOSITOL PHOSPHATE BIOCHEMISTRY [J].
MAJERUS, PW .
ANNUAL REVIEW OF BIOCHEMISTRY, 1992, 61 :225-250
[16]  
MOCHIZUKI H, 1993, J BIOL CHEM, V268, P9143
[17]   INTRACELLULAR SIGNALING BY HYDROLYSIS OF PHOSPHOLIPIDS AND ACTIVATION OF PROTEIN-KINASE-C [J].
NISHIZUKA, Y .
SCIENCE, 1992, 258 (5082) :607-614
[18]  
NISHIZUKA Y, 1989, CANCER, V63, P1892, DOI 10.1002/1097-0142(19890515)63:10<1892::AID-CNCR2820631005>3.0.CO
[19]  
2-Z
[20]   PHORBOL ESTER BINDING TO PROTEIN KINASE-C REQUIRES A CYSTEINE-RICH ZINC-FINGER-LIKE SEQUENCE [J].
ONO, Y ;
FUJII, T ;
IGARASHI, K ;
KUNO, T ;
TANAKA, C ;
KIKKAWA, U ;
NISHIZUKA, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (13) :4868-4871