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PMID: 1448068 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Hydrolysis of phosphatidylcholine is stimulated by Ras proteins during mitogenic signal transduction.

Molecular and cellular biology ·Vol. 12 ·No. 12 ·1992-12-00 ·Pages 5329-35

Cai H, Erhardt P, Szeberényi J, Diaz-Meco MT, Johansen T, Moscat J, Cooper GM

Abstract

We have used a dominant inhibitory ras mutant (Ha-ras Asn-17) to investigate the relationship of Ras proteins to hydrolysis of phosphatidylcholine (PC) in the transduction of mitogenic signals. Expression of Ha-Ras Asn-17 inhibited NIH 3T3 cell proliferation induced by polypeptide growth factors or phorbol esters. In contrast, the mitogenic activity of PC-specific phospholipase C (PC-PLC) was not inhibited by Ha-Ras Asn-17 expression. Similarly, cotransfection with a cloned PC-PLC gene bypassed the block to NIH 3T3 cell proliferation resulting from expression of the inhibitory ras mutant. Hydrolysis of PC can therefore induce cell proliferation in the absence of normal Ras activity, suggesting that PC-derived second messengers may act downstream of Ras in mitogenic signal transduction. This was substantiated by the finding that Ha-Ras Asn-17 expression inhibited growth factor-stimulated hydrolysis of PC. Taken together, these results indicate that PC hydrolysis is a target of Ras during the transduction of growth factor-initiated mitogenic signals.

MeSH Terms
3T3 Cells Animals Blotting, Northern Cell Division Cloning, Molecular Hydrolysis Mice Mitogens/pharmacology Phosphatidylcholines/metabolism Proto-Oncogene Proteins p21(ras)/metabolism Second Messenger Systems Signal Transduction Transfection Type C Phospholipases/genetics,metabolism
Chemicals
Mitogens Phosphatidylcholines Type C Phospholipases Proto-Oncogene Proteins p21(ras)
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Cai H
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Erhardt P
Szeberényi J
Diaz-Meco M T
Johansen T
Moscat J
Cooper G M
References (39)
39 references, click to expand
  1. Phorbol diesters stimulate the accumulation of phosphatidate, phosphatidylethanol, and diacylglycerol in three cell types. Evidence for the indirect formation of phosphatidylcholine-derived diacylglycerol by a phospholipase D pathway and direct formation of diacylglycerol by a phospholipase C pathway.
    J Biol Chem. 1990 Sep 5;265(25):14858-63 PMID: 2394701
  2. Transformation of NIH 3T3 cells by microinjection of Ha-ras p21 protein.
    Nature. 1984 Aug 9-15;310(5977):508-11 PMID: 6611509
  3. Stimulation of phosphatidylcholine hydrolysis, diacylglycerol release, and arachidonic acid production by oncogenic ras is a consequence of protein kinase C activation.
    J Biol Chem. 1989 Oct 5;264(28):16638-43 PMID: 2506180
  4. p21H-ras-induced morphological transformation and increases in c-myc expression are independent of functional protein kinase C.
    EMBO J. 1989 Apr;8(4):1099-104 PMID: 2663469
  5. The structure, expression, and properties of additional members of the protein kinase C family.
    J Biol Chem. 1988 May 15;263(14):6927-32 PMID: 2834397
  6. Requirement for c-ras proteins during viral oncogene transformation.
    Nature. 1986 Apr 10-16;320(6062):540-3 PMID: 2938016
  7. Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation.
    Cell. 1985 Oct;42(3):841-8 PMID: 2996779
  8. Elevated levels of diacylglycerol and decreased phorbol ester sensitivity in ras-transformed fibroblasts.
    Nature. 1987 Jan 22-28;325(6102):359-61 PMID: 3027568
  9. Cloning and sequencing of the gene encoding the phosphatidylcholine-preferring phospholipase C of Bacillus cereus.
    Gene. 1988 May 30;65(2):293-304 PMID: 3137122
  10. Inhibition of NIH 3T3 cell proliferation by a mutant ras protein with preferential affinity for GDP.
    Mol Cell Biol. 1988 Aug;8(8):3235-43 PMID: 3145408
  11. Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells.
    Nature. 1985 Jan 17-23;313(5999):241-3 PMID: 3918269
  12. Microinjection of the oncogene form of the human H-ras (T-24) protein results in rapid proliferation of quiescent cells.
    Cell. 1984 Aug;38(1):109-17 PMID: 6380758
  13. Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases.
    Cell. 1992 Mar 20;68(6):1031-40 PMID: 1312392
  14. Activation of phospholipase D by protein kinase C. Evidence for a phosphorylation-independent mechanism.
    J Biol Chem. 1992 Apr 15;267(11):7199-202 PMID: 1559964
  15. Protein kinase C-independent expression of stromelysin by platelet-derived growth factor, ras oncogene, and phosphatidylcholine-hydrolyzing phospholipase C.
    J Biol Chem. 1991 Nov 25;266(33):22597-602 PMID: 1718997
  16. Mechanism of inhibition of adenylate cyclase by phospholipase C-catalyzed hydrolysis of phosphatidylcholine. Involvement of a pertussis toxin-sensitive G protein and protein kinase C.
    J Biol Chem. 1991 Jan 15;266(2):1170-6 PMID: 1845988
  17. Phospholipase C-mediated hydrolysis of phosphatidylcholine is an important step in PDGF-stimulated DNA synthesis.
    Cell. 1990 Jun 15;61(6):1113-20 PMID: 2112426
  18. Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells.
    Mol Cell Biol. 1990 Oct;10(10):5324-32 PMID: 2118994
  19. Differential metabolism of diradyl glycerol molecular subclasses and molecular species by rabbit brain diglyceride kinase.
    J Biol Chem. 1990 Jul 25;265(21):12280-6 PMID: 2165056
  20. Molecular species analysis of mitogen-stimulated 1,2-diglycerides in fibroblasts. Comparison of alpha-thrombin, epidermal growth factor, and platelet-derived growth factor.
    J Biol Chem. 1990 May 15;265(14):7959-66 PMID: 2335511
  21. Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties.
    Proc Natl Acad Sci U S A. 1989 May;86(9):3099-103 PMID: 2470089
  22. Inositol phosphates and cell signalling.
    Nature. 1989 Sep 21;341(6239):197-205 PMID: 2550825
  23. Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils. Involvement of phosphatidate phosphohydrolase in signal transduction.
    J Biol Chem. 1989 Oct 15;264(29):17069-77 PMID: 2793844
  24. In yeast, RAS proteins are controlling elements of adenylate cyclase.
    Cell. 1985 Jan;40(1):27-36 PMID: 2981630
  25. Inhibition of growth factor-induced differentiation of PC12 cells by microinjection of antibody to ras p21.
    Nature. 1986 Feb 20-26;319(6055):680-2 PMID: 3005866
  26. The molecular heterogeneity of protein kinase C and its implications for cellular regulation.
    Nature. 1988 Aug 25;334(6184):661-5 PMID: 3045562
  27. Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene.
    Nature. 1987 Nov 19-25;330(6145):269-72 PMID: 3313065
  28. Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in a neuronal cell line.
    Nature. 1985 Nov 7-13;318(6041):73-5 PMID: 4058592
  29. ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK.
    Cell. 1992 Mar 20;68(6):1041-50 PMID: 1312393
  30. Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol.
    Oncogene. 1992 Sep;7(9):1867-73 PMID: 1386920
  31. Multiple sources of sn-1,2-diacylglycerol in platelet-derived-growth-factor-stimulated Swiss 3T3 fibroblasts. Evidence for activation of phosphoinositidase C and phosphatidylcholine-specific phospholipase D.
    Biochem J. 1991 Oct 15;279 ( Pt 2):559-65 PMID: 1659382
  32. Quantitative analysis of molecular species of diacylglycerol and phosphatidate formed upon muscarinic receptor activation of human SK-N-SH neuroblastoma cells.
    J Biol Chem. 1991 Dec 5;266(34):22837-46 PMID: 1744076
  33. Dominant inhibitory Ras mutants selectively inhibit the activity of either cellular or oncogenic Ras.
    Mol Cell Biol. 1991 Aug;11(8):4053-64 PMID: 2072908
  34. Signaling through phosphatidylcholine breakdown.
    J Biol Chem. 1990 Jan 5;265(1):1-4 PMID: 2104616
  35. Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells.
    Mol Cell Biol. 1990 Oct;10(10):5314-23 PMID: 2118993
  36. PDGF beta-receptor stimulates tyrosine phosphorylation of GAP and association of GAP with a signaling complex.
    Cell. 1990 Apr 6;61(1):125-33 PMID: 2156626
  37. Binding of GAP to activated PDGF receptors.
    Science. 1990 Mar 30;247(4950):1578-81 PMID: 2157284
  38. Kinetic evidence of a rapid activation of phosphatidylcholine hydrolysis by Ki-ras oncogene. Possible involvement in late steps of the mitogenic cascade.
    J Biol Chem. 1990 Jun 5;265(16):9022-6 PMID: 2188971
  39. PDGF induction of tyrosine phosphorylation of GTPase activating protein.
    Nature. 1989 Dec 7;342(6250):711-4 PMID: 2480526
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.12.5329-5335.1992
Published
1992-12-00
Pages
5329-35
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360470
Subset
IM
Grants
NCI NIH HHS · R01 CA18689 · United States
External Links
PubMed source DOI: 10.1128/mcb.12.12.5329-5335.1992 PMC Full Text View journal details
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