IDENTIFICATION OF A SPECIFIC INS(1,3,4,5)P-4-BINDING PROTEIN AS A MEMBER OF THE GAP1 FAMILY

被引：288
作者：
CULLEN, PJ
HSUAN, JJ
TRUONG, O
LETCHER, AJ
JACKSON, TR
DAWSON, AP
IRVINE, RF
机构：
[1] UNIV E ANGLIA, SCH BIOL SCI, NORWICH NR4 7TJ, NORFOLK, ENGLAND
[2] UCL, SCH MED, LUDWIG INST CANC RES, LONDON W1P 8BT, ENGLAND
[3] UNIV CAMBRIDGE, BABRAHAM INST, DEPT ZOOL, MOLEC SIGNALLING LAB, CAMBRIDGE CB2 3EJ, ENGLAND
来源：
NATURE | 1995年 / 376卷 / 6540期
关键词：
D O I：
10.1038/376527a0
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：
INOSITOL 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P-4) is produced rapidly from inositol 1,4,5-trisphosphate (Ins(1,4,5)P-3) in stimulated cells(1,2). Despite extensive experimentation, no clearly defined cellular function has yet been described for this inositol phosphate. Binding sites specific for Ins(1,3,4,5)P-4 have been identified in several tissues(3,4), and we have purified one such protein to homogeneity(5). Its high affinity for Ins(1,3,4,5)P-4, and its exquisite specificity for this isomeric configuration(5,6), suggest it may be an Ins(1,3,4,5)P-4 receptor. Here we report the cloning and characterization of this protein as a GTPase-activating protein, specifically a member of the GAP family. In vitro it shows GAP activity against both Rap and Ras, but only the Ras GAP activity is inhibited by phospholipids and is specifically stimulated by Ins(1,3,4,5)P-4.
引用
收藏
页码：527 / 530
页数：4
相关论文
共 21 条
[1]   RAPID FORMATION OF INOSITOL 1,3,4,5-TETRAKISPHOSPHATE FOLLOWING MUSCARINIC RECEPTOR STIMULATION OF RAT CEREBRAL CORTICAL SLICES [J].
BATTY, IR ;
NAHORSKI, SR ;
IRVINE, RF .
BIOCHEMICAL JOURNAL, 1985, 232 (01) :211-215
[2]   GENETIC-EVIDENCE FOR THE ROLES OF THE BUD-SITE-SELECTION GENES BUD5 AND BUD2 IN CONTROL OF THE RSR1P (BUD1P) GTPASE IN YEAST [J].
BENDER, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (21) :9926-9929
[3]  
CORVAZIER E, 1991, BIOCHEM J, V281, P323
[4]   SPECIFIC BINDING-SITES FOR INOSITOL 1,3,4,5-TETRAKISPHOSPHATE ARE LOCATED PREDOMINANTLY IN THE PLASMA-MEMBRANES OF HUMAN PLATELETS [J].
CULLEN, PJ ;
PATEL, Y ;
KAKKAR, VV ;
IRVINE, RF ;
AUTHI, KS .
BIOCHEMICAL JOURNAL, 1994, 298 :739-742
[5]   PURIFICATION AND CHARACTERIZATION OF AN INS(1,3,4,5)P-4 BINDING-PROTEIN FROM PIG PLATELETS - POSSIBLE IDENTIFICATION OF A NOVEL NONNEURONAL INS(1,3,4,5)P-4 RECEPTOR [J].
CULLEN, PJ ;
DAWSON, AP ;
IRVINE, RF .
BIOCHEMICAL JOURNAL, 1995, 305 :139-143
[6]   INOSITOL 1,3,4,5-TETRAKISPHOSPHATE BINDING-SITES IN NEURONAL AND NONNEURONAL TISSUES - PROPERTIES, COMPARISONS AND POTENTIAL PHYSIOLOGICAL SIGNIFICANCE [J].
CULLEN, PJ ;
IRVINE, RF .
BIOCHEMICAL JOURNAL, 1992, 288 :149-154
[7]   SPECIFICITY OF THE PURIFIED INOSITOL (1,3,4,5)-TETRAKISPHOSPHATE-BINDING PROTEIN FROM PORCINE PLATELETS [J].
CULLEN, PJ ;
CHUNG, SK ;
CHANG, YT ;
DAWSON, AP ;
IRVINE, RF .
FEBS LETTERS, 1995, 358 (03) :240-242
[8]  
FUKUDA M, 1994, J BIOL CHEM, V269, P29206
[9]   A PUTATIVE RAS GTPASE ACTIVATING PROTEIN ACTS AS A NEGATIVE REGULATOR OF SIGNALING BY THE SEVENLESS RECEPTOR TYROSINE KINASE [J].
GAUL, U ;
MARDON, G ;
RUBIN, GM .
CELL, 1992, 68 (06) :1007-1019
[10]   PH DOMAIN - THE FIRST ANNIVERSARY [J].
GIBSON, TJ ;
HYVONEN, M ;
MUSACCHIO, A ;
SARASTE, M ;
BIRNEY, E .
TRENDS IN BIOCHEMICAL SCIENCES, 1994, 19 (09) :349-353
123