Point mutation in the fibroblast growth factor receptor eliminates phosphatidylinositol hydrolysis without affecting neuronal differentiation of PC12 cells
- PMID: 7514169
Point mutation in the fibroblast growth factor receptor eliminates phosphatidylinositol hydrolysis without affecting neuronal differentiation of PC12 cells
Abstract
Fibroblast growth factors (FGF) stimulate growth arrest and differentiation in rat pheochromocytoma PC12 cells. We examined the role of phosphatidylinositol (PI) hydrolysis in FGF-induced differentiation of PC12 cells by exploring the biological and biochemical activity of a mutant FGF receptor 1 (flg) defective in stimulation of PI hydrolysis. We show that point mutation at Tyr-766 (Y766F) of the FGF receptor prevents tyrosine phosphorylation of phospholipase C gamma and eliminates acidic FGF (aFGF)-induced stimulation of PI hydrolysis in PC12 cells. Treatment of PC12 cells expressing either wild-type or the Y766F mutant with aFGF led to tyrosine phosphorylation of Shc, the association of Shc with GRB2, a shift in the electrophoretic mobility of the Ras guanine nucleotide-releasing factor, Sos (son of sevenless), and enhancement in mitogen-activated protein kinase phosphorylation. Moreover, stimulation with aFGF led to a typical neurite outgrowth of PC12 cells expressing either wild-type or the Y766F FGF receptor mutant. These experiments indicate that PI hydrolysis is not essential for FGF-induced neuronal differentiation of PC12 cells. Moreover, the aFGF-induced Ras signaling pathway, which is essential for PC12 cell differentiation, is not affected by elimination of PI hydrolysis.
Similar articles
-
Reduced activation of RAF-1 and MAP kinase by a fibroblast growth factor receptor mutant deficient in stimulation of phosphatidylinositol hydrolysis.J Biol Chem. 1995 Mar 10;270(10):5065-72. doi: 10.1074/jbc.270.10.5065. J Biol Chem. 1995. PMID: 7534287
-
Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis.Nature. 1992 Aug 20;358(6388):681-4. doi: 10.1038/358681a0. Nature. 1992. PMID: 1379698
-
Internalization of fibroblast growth factor receptor is inhibited by a point mutation at tyrosine 766.J Biol Chem. 1994 Jun 24;269(25):17056-61. J Biol Chem. 1994. PMID: 7516330
-
Point mutation of an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogenesis.Nature. 1992 Aug 20;358(6388):678-81. doi: 10.1038/358678a0. Nature. 1992. PMID: 1379697
-
The FRK/RAK-SHB signaling cascade: a versatile signal-transduction pathway that regulates cell survival, differentiation and proliferation.Curr Mol Med. 2003 Jun;3(4):313-24. doi: 10.2174/1566524033479744. Curr Mol Med. 2003. PMID: 12776987 Review.
Cited by
-
Physiological requirement for both SH2 domains for phospholipase C-gamma1 function and interaction with platelet-derived growth factor receptors.Mol Cell Biol. 1999 Jul;19(7):4961-70. doi: 10.1128/MCB.19.7.4961. Mol Cell Biol. 1999. PMID: 10373546 Free PMC article.
-
Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation.Mol Cell Biol. 1998 Jul;18(7):3966-73. doi: 10.1128/MCB.18.7.3966. Mol Cell Biol. 1998. PMID: 9632781 Free PMC article.
-
soc-2 encodes a leucine-rich repeat protein implicated in fibroblast growth factor receptor signaling.Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6903-8. doi: 10.1073/pnas.95.12.6903. Proc Natl Acad Sci U S A. 1998. PMID: 9618511 Free PMC article.
-
Identification of the cytoplasmic regions of fibroblast growth factor (FGF) receptor 1 which play important roles in induction of neurite outgrowth in PC12 cells by FGF-1.Mol Cell Biol. 1998 Jul;18(7):3762-70. doi: 10.1128/MCB.18.7.3762. Mol Cell Biol. 1998. PMID: 9632759 Free PMC article.
-
Functional roles of fibroblast growth factor receptors (FGFRs) signaling in human cancers.Apoptosis. 2013 Dec;18(12):1447-68. doi: 10.1007/s10495-013-0886-7. Apoptosis. 2013. PMID: 23900974 Free PMC article. Review.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
