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. 1995 Sep 1;130(5):1197–1205. doi: 10.1083/jcb.130.5.1197

Role of phospholipase D in the cAMP signal transduction pathway activated during fibroblast contraction of collagen matrices

PMCID: PMC2120549  PMID: 7657704

Abstract

Fibroblast contraction of stressed collagen matrices results in activation of a cAMP signal transduction pathway. This pathway involves influx of extracellular Ca2+ ions and increased production of arachidonic acid. We report that within 5 min after initiating contraction, a burst of phosphatidic acid release was detected. Phospholipase D was implicated in production of phosphatidic acid based on observation of a transphosphatidylation reaction in the presence of ethanol that resulted in formation of phosphatidylethanol at the expense of phosphatidic acid. Activation of phospholipase D required extracellular Ca2+ ions and was regulated by protein kinase C. Ethanol treatment of cells also inhibited by 60-70% contraction-dependent release of arachidonic acid and cAMP but had no effect on increased cAMP synthesis after addition of exogenous arachidonic acid or on phospholipase A2 activity measured in cell extracts. Moreover, other treatments that inhibited the burst of phosphatidic acid release after contraction--chelating extracellular Ca2+ or down-regulating protein kinase C--also blocked contraction activated cyclic AMP signaling. These results were consistent with the idea that phosphatidic acid production occurred upstream of arachidonic acid in the contraction- activated cAMP signaling pathway.

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Selected References

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  1. Agwu D. E., McCall C. E., McPhail L. C. Regulation of phospholipase D-induced hydrolysis of choline-containing phosphoglycerides by cyclic AMP in human neutrophils. J Immunol. 1991 Jun 1;146(11):3895–3903. [PubMed] [Google Scholar]
  2. Ahmed A., Plevin R., Shoaibi M. A., Fountain S. A., Ferriani R. A., Smith S. K. Basic FGF activates phospholipase D in endothelial cells in the absence of inositol-lipid hydrolysis. Am J Physiol. 1994 Jan;266(1 Pt 1):C206–C212. doi: 10.1152/ajpcell.1994.266.1.C206. [DOI] [PubMed] [Google Scholar]
  3. Allen A. C., Gammon C. M., Ousley A. H., McCarthy K. D., Morell P. Bradykinin stimulates arachidonic acid release through the sequential actions of an sn-1 diacylglycerol lipase and a monoacylglycerol lipase. J Neurochem. 1992 Mar;58(3):1130–1139. doi: 10.1111/j.1471-4159.1992.tb09372.x. [DOI] [PubMed] [Google Scholar]
  4. Arem A. J., Madden J. W. Effects of stress on healing wounds: I. Intermittent noncyclical tension. J Surg Res. 1976 Feb;20(2):93–102. doi: 10.1016/0022-4804(76)90104-9. [DOI] [PubMed] [Google Scholar]
  5. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  6. BREMER J. CARNITINE IN INTERMEDIARY METABOLISM. THE BIOSYNTHESIS OF PALMITYLCARNITINE BY CELL SUBFRACTIONS. J Biol Chem. 1963 Aug;238:2774–2779. [PubMed] [Google Scholar]
  7. Balsinde J., Diez E., Mollinedo F. Arachidonic acid release from diacylglycerol in human neutrophils. Translocation of diacylglycerol-deacylating enzyme activities from an intracellular pool to plasma membrane upon cell activation. J Biol Chem. 1991 Aug 25;266(24):15638–15643. [PubMed] [Google Scholar]
  8. Billah M. M., Eckel S., Mullmann T. J., Egan R. W., Siegel M. I. 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):17069–17077. [PubMed] [Google Scholar]
  9. Billah M. M., Lapetina E. G., Cuatrecasas P. Phospholipase A2 activity specific for phosphatidic acid. A possible mechanism for the production of arachidonic acid in platelets. J Biol Chem. 1981 Jun 10;256(11):5399–5403. [PubMed] [Google Scholar]
  10. Billah M. M. Phospholipase D and cell signaling. Curr Opin Immunol. 1993 Feb;5(1):114–123. doi: 10.1016/0952-7915(93)90090-f. [DOI] [PubMed] [Google Scholar]
  11. Bjerve K. S., Daae L. N., Bremer J. The selective loss of lysophospholipids in some commonly used lipid-extraction procedures. Anal Biochem. 1974 Mar;58(1):238–245. doi: 10.1016/0003-2697(74)90463-1. [DOI] [PubMed] [Google Scholar]
  12. Boarder M. R. A role for phospholipase D in control of mitogenesis. Trends Pharmacol Sci. 1994 Feb;15(2):57–62. doi: 10.1016/0165-6147(94)90111-2. [DOI] [PubMed] [Google Scholar]
  13. Brooks R. C., McCarthy K. D., Lapetina E. G., Morell P. Receptor-stimulated phospholipase A2 activation is coupled to influx of external calcium and not to mobilization of intracellular calcium in C62B glioma cells. J Biol Chem. 1989 Nov 25;264(33):20147–20153. [PubMed] [Google Scholar]
  14. Brown H. A., Gutowski S., Moomaw C. R., Slaughter C., Sternweis P. C. ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity. Cell. 1993 Dec 17;75(6):1137–1144. doi: 10.1016/0092-8674(93)90323-i. [DOI] [PubMed] [Google Scholar]
  15. Brown H. A., Lazarowski E. R., Boucher R. C., Harden T. K. Evidence that UTP and ATP regulate phospholipase C through a common extracellular 5'-nucleotide receptor in human airway epithelial cells. Mol Pharmacol. 1991 Nov;40(5):648–655. [PubMed] [Google Scholar]
  16. Burch R. M., Axelrod J. Dissociation of bradykinin-induced prostaglandin formation from phosphatidylinositol turnover in Swiss 3T3 fibroblasts: evidence for G protein regulation of phospholipase A2. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6374–6378. doi: 10.1073/pnas.84.18.6374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Burgering B. M., Pronk G. J., van Weeren P. C., Chardin P., Bos J. L. cAMP antagonizes p21ras-directed activation of extracellular signal-regulated kinase 2 and phosphorylation of mSos nucleotide exchange factor. EMBO J. 1993 Nov;12(11):4211–4220. doi: 10.1002/j.1460-2075.1993.tb06105.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Burgess L. P., Morin G. V., Rand M., Vossoughi J., Hollinger J. O. Wound healing. Relationship of wound closing tension to scar width in rats. Arch Otolaryngol Head Neck Surg. 1990 Jul;116(7):798–802. doi: 10.1001/archotol.1990.01870070046008. [DOI] [PubMed] [Google Scholar]
  19. Burgoyne R. D., Morgan A. The control of free arachidonic acid levels. Trends Biochem Sci. 1990 Oct;15(10):365–366. doi: 10.1016/0968-0004(90)90227-3. [DOI] [PubMed] [Google Scholar]
  20. Carnero A., Cuadrado A., del Peso L., Lacal J. C. Activation of type D phospholipase by serum stimulation and ras-induced transformation in NIH3T3 cells. Oncogene. 1994 May;9(5):1387–1395. [PubMed] [Google Scholar]
  21. Channon J. Y., Leslie C. C. A calcium-dependent mechanism for associating a soluble arachidonoyl-hydrolyzing phospholipase A2 with membrane in the macrophage cell line RAW 264.7. J Biol Chem. 1990 Apr 5;265(10):5409–5413. [PubMed] [Google Scholar]
  22. Clark J. D., Lin L. L., Kriz R. W., Ramesha C. S., Sultzman L. A., Lin A. Y., Milona N., Knopf J. L. A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. Cell. 1991 Jun 14;65(6):1043–1051. doi: 10.1016/0092-8674(91)90556-e. [DOI] [PubMed] [Google Scholar]
  23. Clark R. B., Salmon D. M., Honeyman T. W. Phosphatidic acid inhibition of PGE1-stimulated cAMP accumulation in WI-38 fibroblasts: similarities with carbachol inhibition. J Cyclic Nucleotide Res. 1980;6(1):37–49. [PubMed] [Google Scholar]
  24. Cockcroft S., Thomas G. M., Fensome A., Geny B., Cunningham E., Gout I., Hiles I., Totty N. F., Truong O., Hsuan J. J. Phospholipase D: a downstream effector of ARF in granulocytes. Science. 1994 Jan 28;263(5146):523–526. doi: 10.1126/science.8290961. [DOI] [PubMed] [Google Scholar]
  25. Cook S. J., Wakelam M. J. Epidermal growth factor increases sn-1,2-diacylglycerol levels and activates phospholipase D-catalysed phosphatidylcholine breakdown in Swiss 3T3 cells in the absence of inositol-lipid hydrolysis. Biochem J. 1992 Jul 1;285(Pt 1):247–253. doi: 10.1042/bj2850247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Daniels K., Solursh M. Modulation of chondrogenesis by the cytoskeleton and extracellular matrix. J Cell Sci. 1991 Oct;100(Pt 2):249–254. doi: 10.1242/jcs.100.2.249. [DOI] [PubMed] [Google Scholar]
  27. Davies P. F., Tripathi S. C. Mechanical stress mechanisms and the cell. An endothelial paradigm. Circ Res. 1993 Feb;72(2):239–245. doi: 10.1161/01.res.72.2.239. [DOI] [PubMed] [Google Scholar]
  28. Diez E., Mong S. Purification of a phospholipase A2 from human monocytic leukemic U937 cells. Calcium-dependent activation and membrane association. J Biol Chem. 1990 Aug 25;265(24):14654–14661. [PubMed] [Google Scholar]
  29. Dubyak G. R., Schomisch S. J., Kusner D. J., Xie M. Phospholipase D activity in phagocytic leucocytes is synergistically regulated by G-protein- and tyrosine kinase-based mechanisms. Biochem J. 1993 May 15;292(Pt 1):121–128. doi: 10.1042/bj2920121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Erdos T., Butler-Browne G. S., Rappaport L. Mechanogenetic regulation of transcription. Biochimie. 1991 Sep;73(9):1219–1231. doi: 10.1016/0300-9084(91)90007-n. [DOI] [PubMed] [Google Scholar]
  31. Etscheid B. G., Villereal M. L. Coupling of bradykinin receptors to phospholipase C in cultured fibroblasts is mediated by a G-protein. J Cell Physiol. 1989 Aug;140(2):264–271. doi: 10.1002/jcp.1041400211. [DOI] [PubMed] [Google Scholar]
  32. Exton J. H. Phosphatidylcholine breakdown and signal transduction. Biochim Biophys Acta. 1994 Apr 14;1212(1):26–42. doi: 10.1016/0005-2760(94)90186-4. [DOI] [PubMed] [Google Scholar]
  33. Fisher G. J., Henderson P. A., Voorhees J. J., Baldassare J. J. Epidermal growth factor-induced hydrolysis of phosphatidylcholine by phospholipase D and phospholipase C in human dermal fibroblasts. J Cell Physiol. 1991 Feb;146(2):309–317. doi: 10.1002/jcp.1041460216. [DOI] [PubMed] [Google Scholar]
  34. Garcia J. G., Fenton J. W., 2nd, Natarajan V. Thrombin stimulation of human endothelial cell phospholipase D activity. Regulation by phospholipase C, protein kinase C, and cyclic adenosine 3'5'-monophosphate. Blood. 1992 Apr 15;79(8):2056–2067. [PubMed] [Google Scholar]
  35. Graves L. M., Bornfeldt K. E., Raines E. W., Potts B. C., Macdonald S. G., Ross R., Krebs E. G. Protein kinase A antagonizes platelet-derived growth factor-induced signaling by mitogen-activated protein kinase in human arterial smooth muscle cells. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10300–10304. doi: 10.1073/pnas.90.21.10300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Grinnell F. Fibroblasts, myofibroblasts, and wound contraction. J Cell Biol. 1994 Feb;124(4):401–404. doi: 10.1083/jcb.124.4.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Gruchalla R. S., Dinh T. T., Kennerly D. A. An indirect pathway of receptor-mediated 1,2-diacylglycerol formation in mast cells. I. IgE receptor-mediated activation of phospholipase D. J Immunol. 1990 Mar 15;144(6):2334–2342. [PubMed] [Google Scholar]
  38. Harris A. K., Stopak D., Wild P. Fibroblast traction as a mechanism for collagen morphogenesis. Nature. 1981 Mar 19;290(5803):249–251. doi: 10.1038/290249a0. [DOI] [PubMed] [Google Scholar]
  39. He Y., Grinnell F. Stress relaxation of fibroblasts activates a cyclic AMP signaling pathway. J Cell Biol. 1994 Jul;126(2):457–464. doi: 10.1083/jcb.126.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Heidemann S. R., Buxbaum R. E. Tension as a regulator and integrator of axonal growth. Cell Motil Cytoskeleton. 1990;17(1):6–10. doi: 10.1002/cm.970170103. [DOI] [PubMed] [Google Scholar]
  41. Ingber D. E. The riddle of morphogenesis: a question of solution chemistry or molecular cell engineering? Cell. 1993 Dec 31;75(7):1249–1252. doi: 10.1016/0092-8674(93)90612-t. [DOI] [PubMed] [Google Scholar]
  42. Kramer R. M., Roberts E. F., Manetta J., Putnam J. E. The Ca2(+)-sensitive cytosolic phospholipase A2 is a 100-kDa protein in human monoblast U937 cells. J Biol Chem. 1991 Mar 15;266(8):5268–5272. [PubMed] [Google Scholar]
  43. Lee T. L., Lin Y. C., Mochitate K., Grinnell F. Stress-relaxation of fibroblasts in collagen matrices triggers ectocytosis of plasma membrane vesicles containing actin, annexins II and VI, and beta 1 integrin receptors. J Cell Sci. 1993 May;105(Pt 1):167–177. doi: 10.1242/jcs.105.1.167. [DOI] [PubMed] [Google Scholar]
  44. Lin L. L., Wartmann M., Lin A. Y., Knopf J. L., Seth A., Davis R. J. cPLA2 is phosphorylated and activated by MAP kinase. Cell. 1993 Jan 29;72(2):269–278. doi: 10.1016/0092-8674(93)90666-e. [DOI] [PubMed] [Google Scholar]
  45. Lin Y. C., Grinnell F. Decreased level of PDGF-stimulated receptor autophosphorylation by fibroblasts in mechanically relaxed collagen matrices. J Cell Biol. 1993 Aug;122(3):663–672. doi: 10.1083/jcb.122.3.663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Malcolm K. C., Ross A. H., Qiu R. G., Symons M., Exton J. H. Activation of rat liver phospholipase D by the small GTP-binding protein RhoA. J Biol Chem. 1994 Oct 21;269(42):25951–25954. [PubMed] [Google Scholar]
  47. Malek A. M., Greene A. L., Izumo S. Regulation of endothelin 1 gene by fluid shear stress is transcriptionally mediated and independent of protein kinase C and cAMP. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5999–6003. doi: 10.1073/pnas.90.13.5999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Mattila P., Ustinov J., Renkonen R. Interferon-gamma induces a phospholipase D-dependent release of arachidonic acid from endothelial cell membranes: a mechanism for protein kinase C activation. Scand J Immunol. 1993 Aug;38(2):197–200. doi: 10.1111/j.1365-3083.1993.tb01713.x. [DOI] [PubMed] [Google Scholar]
  49. Mochitate K., Pawelek P., Grinnell F. Stress relaxation of contracted collagen gels: disruption of actin filament bundles, release of cell surface fibronectin, and down-regulation of DNA and protein synthesis. Exp Cell Res. 1991 Mar;193(1):198–207. doi: 10.1016/0014-4827(91)90556-a. [DOI] [PubMed] [Google Scholar]
  50. Moehren G., Gustavsson L., Hoek J. B. Activation and desensitization of phospholipase D in intact rat hepatocytes. J Biol Chem. 1994 Jan 14;269(2):838–848. [PubMed] [Google Scholar]
  51. Murayama T., Ui M. Phosphatidic acid may stimulate membrane receptors mediating adenylate cyclase inhibition and phospholipid breakdown in 3T3 fibroblasts. J Biol Chem. 1987 Apr 25;262(12):5522–5529. [PubMed] [Google Scholar]
  52. Nakagawa S., Pawelek P., Grinnell F. Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness. Exp Cell Res. 1989 Jun;182(2):572–582. doi: 10.1016/0014-4827(89)90260-7. [DOI] [PubMed] [Google Scholar]
  53. Nishiyama T., Akutsu N., Horii I., Nakayama Y., Ozawa T., Hayashi T. Response to growth factors of human dermal fibroblasts in a quiescent state owing to cell-matrix contact inhibition. Matrix. 1991 Apr;11(2):71–75. doi: 10.1016/s0934-8832(11)80210-6. [DOI] [PubMed] [Google Scholar]
  54. Paul A., Plevin R. Evidence against a role for phospholipase D in mitogenesis. Trends Pharmacol Sci. 1994 Jun;15(6):174–175. doi: 10.1016/0165-6147(94)90140-6. [DOI] [PubMed] [Google Scholar]
  55. Reinhart W. H. Shear-dependence of endothelial functions. Experientia. 1994 Feb 15;50(2):87–93. doi: 10.1007/BF01984940. [DOI] [PubMed] [Google Scholar]
  56. Resnick N., Collins T., Atkinson W., Bonthron D. T., Dewey C. F., Jr, Gimbrone M. A., Jr Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4591–4595. doi: 10.1073/pnas.90.10.4591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Rindlisbacher B., Reist M., Zahler P. Diacylglycerol breakdown in plasma membranes of bovine chromaffin cells is a two-step mechanism mediated by a diacylglycerol lipase and a monoacylglycerol lipase. Biochim Biophys Acta. 1987 Dec 11;905(2):349–357. doi: 10.1016/0005-2736(87)90463-9. [DOI] [PubMed] [Google Scholar]
  58. Ryan T. J. Biochemical consequences of mechanical forces generated by distention and distortion. J Am Acad Dermatol. 1989 Jul;21(1):115–130. doi: 10.1016/s0190-9622(89)70156-0. [DOI] [PubMed] [Google Scholar]
  59. Sadoshima J., Izumo S. Mechanical stretch rapidly activates multiple signal transduction pathways in cardiac myocytes: potential involvement of an autocrine/paracrine mechanism. EMBO J. 1993 Apr;12(4):1681–1692. doi: 10.1002/j.1460-2075.1993.tb05813.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sadoshima J., Xu Y., Slayter H. S., Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell. 1993 Dec 3;75(5):977–984. doi: 10.1016/0092-8674(93)90541-w. [DOI] [PubMed] [Google Scholar]
  61. Salomon Y. Cellular responsiveness to hormones and neurotransmitters: conversion of [3H]adenine to [3H]cAMP in cell monolayers, cell suspensions, and tissue slices. Methods Enzymol. 1991;195:22–28. doi: 10.1016/0076-6879(91)95151-9. [DOI] [PubMed] [Google Scholar]
  62. Sevetson B. R., Kong X., Lawrence J. C., Jr Increasing cAMP attenuates activation of mitogen-activated protein kinase. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10305–10309. doi: 10.1073/pnas.90.21.10305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Simpson D. G., Carver W., Borg T. K., Terracio L. Role of mechanical stimulation in the establishment and maintenance of muscle cell differentiation. Int Rev Cytol. 1994;150:69–94. doi: 10.1016/s0074-7696(08)61537-5. [DOI] [PubMed] [Google Scholar]
  64. Thomas L. M., Holub B. J. Eicosanoid-dependent and -independent formation of individual [14C]stearoyl-labelled lysophospholipids in collagen-stimulated human platelets. Biochim Biophys Acta. 1991 Jan 4;1081(1):92–98. doi: 10.1016/0005-2760(91)90255-g. [DOI] [PubMed] [Google Scholar]
  65. Thompson N. T., Bonser R. W., Garland L. G. Receptor-coupled phospholipase D and its inhibition. Trends Pharmacol Sci. 1991 Nov;12(11):404–408. doi: 10.1016/0165-6147(91)90617-2. [DOI] [PubMed] [Google Scholar]
  66. Thyberg J., Hedin U., Sjölund M., Palmberg L., Bottger B. A. Regulation of differentiated properties and proliferation of arterial smooth muscle cells. Arteriosclerosis. 1990 Nov-Dec;10(6):966–990. doi: 10.1161/01.atv.10.6.966. [DOI] [PubMed] [Google Scholar]
  67. Tingström A., Heldin C. H., Rubin K. Regulation of fibroblast-mediated collagen gel contraction by platelet-derived growth factor, interleukin-1 alpha and transforming growth factor-beta 1. J Cell Sci. 1992 Jun;102(Pt 2):315–322. doi: 10.1242/jcs.102.2.315. [DOI] [PubMed] [Google Scholar]
  68. Tomasek J. J., Haaksma C. J., Eddy R. J., Vaughan M. B. Fibroblast contraction occurs on release of tension in attached collagen lattices: dependency on an organized actin cytoskeleton and serum. Anat Rec. 1992 Mar;232(3):359–368. doi: 10.1002/ar.1092320305. [DOI] [PubMed] [Google Scholar]
  69. Tyagi S. R., Olson S. C., Burnham D. N., Lambeth J. D. Cyclic AMP-elevating agents block chemoattractant activation of diradylglycerol generation by inhibiting phospholipase D activation. J Biol Chem. 1991 Feb 25;266(6):3498–3504. [PubMed] [Google Scholar]
  70. Uings I. J., Thompson N. T., Randall R. W., Spacey G. D., Bonser R. W., Hudson A. T., Garland L. G. Tyrosine phosphorylation is involved in receptor coupling to phospholipase D but not phospholipase C in the human neutrophil. Biochem J. 1992 Feb 1;281(Pt 3):597–600. doi: 10.1042/bj2810597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Vandenburgh H. H. Mechanical forces and their second messengers in stimulating cell growth in vitro. Am J Physiol. 1992 Mar;262(3 Pt 2):R350–R355. doi: 10.1152/ajpregu.1992.262.3.R350. [DOI] [PubMed] [Google Scholar]
  72. Wang D. J., Huang N. N., Heller E. J., Heppel L. A. A novel synergistic stimulation of Swiss 3T3 cells by extracellular ATP and mitogens with opposite effects on cAMP levels. J Biol Chem. 1994 Jun 17;269(24):16648–16655. [PubMed] [Google Scholar]
  73. Wang N., Ingber D. E. Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. Biophys J. 1994 Jun;66(6):2181–2189. doi: 10.1016/S0006-3495(94)81014-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Watson P. A. Function follows form: generation of intracellular signals by cell deformation. FASEB J. 1991 Apr;5(7):2013–2019. doi: 10.1096/fasebj.5.7.1707019. [DOI] [PubMed] [Google Scholar]
  75. Wilson E., Mai Q., Sudhir K., Weiss R. H., Ives H. E. Mechanical strain induces growth of vascular smooth muscle cells via autocrine action of PDGF. J Cell Biol. 1993 Nov;123(3):741–747. doi: 10.1083/jcb.123.3.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Wu J., Dent P., Jelinek T., Wolfman A., Weber M. J., Sturgill T. W. Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3',5'-monophosphate. Science. 1993 Nov 12;262(5136):1065–1069. doi: 10.1126/science.7694366. [DOI] [PubMed] [Google Scholar]
  77. van Blitterswijk W. J., Hilkmann H., de Widt J., van der Bend R. L. Phospholipid metabolism in bradykinin-stimulated human fibroblasts. II. Phosphatidylcholine breakdown by phospholipases C and D; involvement of protein kinase C. J Biol Chem. 1991 Jun 5;266(16):10344–10350. [PubMed] [Google Scholar]

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