EFFECT OF PHOSPHOLIPASE-C-GAMMA OVEREXPRESSION ON PDGF-INDUCED 2ND MESSENGERS AND MITOGENESIS

被引:170
作者
MARGOLIS, B
ZILBERSTEIN, A
FRANKS, C
FELDER, S
KREMER, S
ULLRICH, A
RHEE, SG
SKORECKI, K
SCHLESSINGER, J
机构
[1] UNIV TORONTO,MEMBRANE BIOL GRP,TORONTO M5S 1A1,ONTARIO,CANADA
[2] MAX PLANCK INST BIOCHEM,W-8033 MARTINSRIED,GERMANY
[3] NHLBI,BETHESDA,MD 20892
关键词
D O I
10.1126/science.2333512
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
Platelet-derived growth factor (PDGF) stimulates phospholipase C (PLC) activity and the phosphorylation of the γ isozyme of PLC (PLC-γ) in vitro and in living cells. The role of PLC-γ in the phosphoinositide signaling pathway was addressed by examining the effect of overexpression of PLC-γ on cellular responses to PDGF. Overexpression of PLC-γ correlated with PDGF-induced tyrosine phosphorylation of PLC-γ and with PDGF-induced breakdown of phosphatidylinositol 4,5-bisphosphate (PIP 2). However, neither bradykinin- nor lysophosphatidic acid - induced phosphoinositide metabolism was enhanced in the transfected cells, suggesting that the G protein - coupled phosphoinositide responses to these ligands are mediated by other PLC isozymes. The enhanced PDGF-induced generation of inositol trisphosphate (IP3) did not enhance intracellular calcium signaling or influence PDGF-induced DNA synthesis. Thus, enzymes other than PLC-γ may limit PDGF-induced calcium signaling and DNA synthesis. Alternatively, PDGF-induced calcium signaling and DNA synthesis may use biochemical pathways other than phosphoinositide metabolism for signal transduction.
引用
收藏
页码:607 / 610
页数:4
相关论文
共 29 条
[1]   INOSITOL PHOSPHATES AND CELL SIGNALING [J].
BERRIDGE, MJ ;
IRVINE, RF .
NATURE, 1989, 341 (6239) :197-205
[2]  
BESTERMAN JM, 1986, J BIOL CHEM, V261, P723
[3]  
BLAKELEY DM, 1989, BIOCHEM J, V258, P1977
[5]   INOSITOL 1,3,4,5-TETRAKISPHOSPHATE AND NOT PHOSPHATIDYLINOSITOL 3,4--BISPHOSPHATE IS THE PROBABLE PRECURSOR OF INOSITOL 1,3,4-TRISPHOSPHATE IN AGONIST-STIMULATED PAROTID-GLAND [J].
DOWNES, CP ;
HAWKINS, PT ;
IRVINE, RF .
BIOCHEMICAL JOURNAL, 1986, 238 (02) :501-506
[6]   PHOSPHOLIPASE C-GAMMA A SUBSTRATE FOR PDGF RECEPTOR KINASE, IS NOT PHOSPHORYLATED ON TYROSINE DURING THE MITOGENIC RESPONSE TO CSF-1 [J].
DOWNING, JR ;
MARGOLIS, BL ;
ZILBERSTEIN, A ;
ASHMUN, RA ;
ULLRICH, A ;
SHERR, CJ ;
SCHLESSINGER, J .
EMBO JOURNAL, 1989, 8 (11) :3345-3350
[7]  
HASEGAWASASAKI H, 1988, J BIOL CHEM, V263, P12970
[8]   EFFECTS OF BOMBESIN AND INSULIN ON INOSITOL (1,4,5)TRISPHOSPHATE AND INOSITOL (1,3,4)TRISPHOSPHATE FORMATION IN SWISS 3T3-CELLS [J].
HESLOP, JP ;
BLAKELEY, DM ;
BROWN, KD ;
IRVINE, RF ;
BERRIDGE, MJ .
CELL, 1986, 47 (05) :703-709
[9]   EXPRESSION OF ACIDIC FIBROBLAST GROWTH-FACTOR CDNA CONFERS GROWTH ADVANTAGE AND TUMORIGENESIS TO SWISS 3T3-CELLS [J].
JAYE, M ;
LYALL, RM ;
MUDD, R ;
SCHLESSINGER, J ;
SARVER, N .
EMBO JOURNAL, 1988, 7 (04) :963-969
[10]  
KERMER S, 1989, J CELL PHYSL, V138, P97