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Role of Nonreceptor Protein Tyrosine Kinases During Phospholipase C-γ1-related Uterine Contractions in the Rat

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Abstract

Activated phospholipase C1, produced in response to tyrosine phosphorylation, appears to play an important role during uterine contractions. These studies sought to determine which non-receptor protein tyrosine kinases are involved in the activation of phospholipase C1 in rat uterine tissue. In vitro contraction studies were performed utilizing isoform specific protein tyrosine kinase inhibitors. Western blots were performed utilizing antibodies to phosphotyrosine-phospholipase C1, total phospholipase C1, c-Src kinase and Lck kinase. Spontaneous, stretch-stimulated, and bpV(phen) (tyrosine phosphatase inhibitor) enhanced uterine contractions were significantly suppressed in response to Damnacanthal (Lck kinase inhibitor) and PP1 (c-Src kinase inhibitor). Damnacanthal and PP1 also significantly suppressed bpV(phen)-enhanced tyrosine phosphorylation of phospholipase C1. Western blots confirmed expression of Lck kinase and c-Src kinase in uterine tissue. In conclusion, the Lck and c-Src kinases appear to play an important role in regulating tyrosine phosphorylation of phospholipase C1 and contractile activity in the rat uterus.

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References

  1. Phillippe M, Sweet LM, Engle D. The role of phospholipase Cgammal tyrosine phosphorylation during phasic myometrial contractions. Am J Obstet Gynecol. 2007;196:179.e1-e7.

    Article  Google Scholar 

  2. Sekiya F, Bae YS, Rhee SG. Regulation of phospholipase C isozymes: activation of phospholipase C-gamma in the absence of tyrosine-phosphorylation. Chem Phys Lipids. 1999;98:3–11.

    Article  CAS  Google Scholar 

  3. Carpenter G, Ji Q. Phospholipase C-gamma as a signal-transducing element. Exp Cell Res. 1999;253:15–24.

    Article  CAS  Google Scholar 

  4. Bieber E, Stratman T, Sanseverino M, Sangueza J, Phillippe M. Phosphatidylinositol-specific phospholipase C isoform expression in pregnant and nonpregnant rat myometrial tissue. Am J Obstet Gynecol. 1998;178:848–854.

    Article  CAS  Google Scholar 

  5. Kim TT, Saunders T, Bieber E, Phillippe M. Protein expression of phospholipase C in pregnant and nonpregnant rat uterine tissue. Am J Obstet Gynecol. 2001;185:1191–1197.

    Article  CAS  Google Scholar 

  6. Phaneuf S, Carrasco MP, Europe-Finner GN, Hamilton CH, Lopez Bernal A. Multiple G proteins and phospholipase C iso-forms in human myometrial cells: implication for oxytocin action. J Clin Endocrinol Metab. 1996;81:2098–2103.

    CAS  PubMed  Google Scholar 

  7. Schmitz U, Ishida M, Berk BC. Angiotensin II stimulates tyrosine phosphorylation of phospholipase C-gamma-associated proteins. Characterization of a c-Src-dependent 97-kD protein in vascular smooth muscle cells. Circ Res. 1997;81:550–557.

    Article  CAS  Google Scholar 

  8. Boulven I, Robin P, Desmyter C, Harbon S, Leiber D. Differential involvement of Src family kinases in pervanadate-mediated responses in rat myometrial cells. Cell Signal. 2002;14:341–349.

    Article  CAS  Google Scholar 

  9. Brown MT, Cooper JA. Regulation, substrates and functions of src. Biochim Biophys Acta. 1996;1287:121–149.

    PubMed  Google Scholar 

  10. Bjorge JD, Jakymiw A, Fujita DJ. Selected glimpses into the activation and function of Src kinase. Oncogene. 2000;19: 5620–5635.

    Article  CAS  Google Scholar 

  11. Tokmakov AA, Sato KI, Iwasaki T, Fukami Y. Src kinase induces calcium release in Xenopus egg extracts via PLCgamma and IP3-dependent mechanism. Cell Calcium. 2002;32:11–20.

    Article  CAS  Google Scholar 

  12. Pisegna S, Zingoni A, Pirozzi G, et al. Src-dependent Syk activation controls CD69-mediated signaling and function on human NK cells. J Immunol. 2002;169:68–74.

    Article  CAS  Google Scholar 

  13. Liao F, Shin HS, Rhee SG. In vitro tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2 by src-family protein tyrosine kinases. Biochem Biophys Res Commun. 1993;191:1028–1033.

    Article  CAS  Google Scholar 

  14. Nakao F, Kobayashi S, Mogami K, et al. Involvement of Src family protein tyrosine kinases in Ca(2+) sensitization of coronary artery contraction mediated by a sphingosylphosphorylcholine-Rho-kinase pathway. Circ Res. 2002;91: 953–960.

    Article  CAS  Google Scholar 

  15. Knock GA, Shaifta Y, Snetkov VA, et al. Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery. Cardiovasc Res. 2008;77:570–579.

    Article  CAS  Google Scholar 

  16. Aoki K, Parent A, Zhang J. Mechanism of damnacanthal-induced [Ca(2+)](i) elevation in human dermal fibroblasts. Eur J Pharmacol. 2000;387:119–124.

    Article  CAS  Google Scholar 

  17. Lee HM, Won KJ, Kim J, et al. Endothelin-1 induces contraction via a Syk-mediated p38 mitogen-activated protein kinase pathway in rat aortic smooth muscle. J Pharmacol Sci. 2007;103:427–433.

    Article  CAS  Google Scholar 

  18. Blake RA, Broome MA, Liu X, et al. SU6656, a selective src family kinase inhibitor, used to probe growth factor signaling. Mol Cell Biol. 2000;20:9018–9027.

    Article  CAS  Google Scholar 

  19. Rhee SG. Regulation of phosphoinositide-specific phospholipase C. Annu Rev Biochem. 2001;70:281–312.

    Article  CAS  Google Scholar 

  20. Gervais FG, Chow LM, Lee JM, Branton PE, Veillette A. The SH2 domain is required for stable phosphorylation of p56lck at tyrosine 505, the negative regulatory site. Mol Cell Biol. 1993;13:7112–7121.

    Article  CAS  Google Scholar 

  21. Ramos-Morales F, Doute M, Fischer S. P56lck: a transducing protein that binds to SH2 containing proteins and to phosphotyrosine containing proteins. Cell Mol Biol (Noisy-le-grand). 1994;40:695–700.

    CAS  Google Scholar 

  22. Ozdener F, Dangelmaier C, Ashby B, Kunapuli SP, Daniel JL. Activation of phospholipase Cgamma2 by tyrosine phosphorylation. Mol Pharmacol. 2002;62:672–679.

    Article  CAS  Google Scholar 

  23. Veri MC, DeBell KE, Seminario MC, et al. Membrane raft-dependent regulation of phospholipase Cgamma-1 activation in T lymphocytes. Mol Cell Biol. 2001;21:6939–6950.

    Article  CAS  Google Scholar 

  24. Thomas SM, Brugge JS. Cellular functions regulated by Src family kinases. Annu Rev Cell Dev Biol. 1997;13:513–609.

    Article  CAS  Google Scholar 

  25. Hollenberg MD. Tyrosine kinase-mediated signal transduction pathways and the actions of polypeptide growth factors and G-protein-coupled agonists in smooth muscle. Mol Cell Biochem. 1995;149–150:77–85.

    Article  Google Scholar 

  26. Oda Y, Renaux B, Bjorge J, Saifeddine M, Fujita DJ, Hollenberg MD. cSrc is a major cytosolic tyrosine kinase in vascular tissue. Can J Physiol Pharmacol. 1999;77:606–617.

    Article  CAS  Google Scholar 

  27. Hu XQ, Singh N, Mukhopadhyay D, Akbarali HI. Modulation of voltage-dependent Ca2+ channels in rabbit colonic smooth muscle cells by c-Src and focal adhesion kinase. J Biol Chem. 1998;273:5337–5342.

    Article  CAS  Google Scholar 

  28. Che Q, Carmines PK. Src family kinase involvement in rat preglomerular microvascular contractile and [Ca2+]i responses to ANG II. Am J Physiol Renal Physiol. 2005;288: F658-F664.

    Article  CAS  Google Scholar 

  29. Palmier B, Leiber D, Harbon S. Pervanadate mediated an increased generation of inositol phosphates and tension in rat myometrium. Activation and phosphorylation of phospholipase C-gamma 1. Biol Reprod. 1996;54:1383–1389.

    Article  CAS  Google Scholar 

  30. Kirber MT, Walsh, JV Jr, Singer JJ. Stretch-activated ion channels in smooth muscle: a mechanism for the initiation of stretch-induced contraction. Pflugers Arch. 1988;412:339–345.

    Article  CAS  Google Scholar 

  31. Kasai Y, Tsutsumi O, Taketani Y, Endo M, Iino M. Stretch-induced enhancement of contractions in uterine smooth muscle of rats. J Physiol. 1995;486(pt 2):373–384.

    Article  CAS  Google Scholar 

  32. Tanaka Y, Hata S, Ishiro H, Ishii K, Nakayama K. Stretching releases Ca2+ from intracellular storage sites in canine cerebral arteries. Can J Physiol Pharmacol. 1994;72:19–24.

    Article  CAS  Google Scholar 

  33. Tanaka Y, Hata S, Ishiro H, Ishii K, Nakayama K. Quick stretch increases the production of inositol 1,4,5-trisphosphate (IP3) in porcine coronary artery. Life Sci. 1994;55:227–235.

    Article  CAS  Google Scholar 

  34. Matsumoto H, Baron CB, Coburn RF. Smooth muscle stretch-activated phospholipase C activity. Am J Physiol. 1995;268:C458-C465.

    Article  CAS  Google Scholar 

  35. Oeckler RA, Kaminski PM, Wolin MS. Stretch enhances contraction of bovine coronary arteries via an NAD(P)H oxidase-mediated activation of the extracellular signal-regulated kinase mitogen-activated protein kinase cascade. Circ Res. 2003;92:23–31.

    Article  CAS  Google Scholar 

  36. Oldenhof AD, Shynlova OP, Liu M, Langille BL, Lye SJ. Mitogen-activated protein kinases mediate stretch-induced c-fos mRNA expression in myometrial smooth muscle cells. Am J Physiol Cell Physiol. 2002;283:C1530-C1539.

    Article  CAS  Google Scholar 

  37. Li Y, Gallant C, Malek S, Morgan KG. Focal adhesion signaling is required for myometrial ERK activation and contractile phenotype switch before labor. J Cell Biochem. 2007;100:129–140.

    Article  CAS  Google Scholar 

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Correspondence to Mark Phillippe MD, MHCM.

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Phillippe, M., Sweet, L.M., Bradley, D.F. et al. Role of Nonreceptor Protein Tyrosine Kinases During Phospholipase C-γ1-related Uterine Contractions in the Rat. Reprod. Sci. 16, 265–273 (2009). https://doi.org/10.1177/1933719108327598

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