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. 1997 Apr 15;323(Pt 2):313–319. doi: 10.1042/bj3230313

Mitogen-activated protein kinase phosphatase 1 inhibits the stimulation of gene expression by hypertrophic agonists in cardiac myocytes.

S J Fuller 1, E L Davies 1, J Gillespie-Brown 1, H Sun 1, N K Tonks 1
PMCID: PMC1218321  PMID: 9163318

Abstract

The effect of constitutive expression of mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) on gene expression in response to hypertrophic agonists was examined in cultured neonatal rat ventricular myocytes. Luciferase (LUX) reporter genes linked to promoters for atrial natriuretic factor, ventricular myosin light chain 2, beta-myosin heavy chain, skeletal muscle alpha-actin (SkM alpha-actin) and serum response element-regulated c-fos (c-fos-SRE) were transfected into cardiomyocytes. Phenylephrine (PE; 10 microM), phorbol 12-myristate 13-acetate (1 microM) and endothelin 1 (10 nM) stimulated the expression of these various reporter genes by 2. 5-20-fold. MKP-1 inhibited these effects by 60-85%. In contrast, MKP-1 had no effect on the expression of a constitutively active Rous sarcoma virus-LUX reporter gene. A catalytically inactive mutant MKP-1CS (cysteine-->serine mutation) and the broad-specificity protein tyrosine phosphatase 1B (PTP-1B) had no significant effect on any reporter gene tested. MKP-1 had much less effect on the morphological features accompanying agonist-induced cardiac hypertrophy. PE (10 microM) increased myocyte area by 59% but this effect was only decreased by one-third by MKP-1 and was also partly decreased (by 25%) by expression of PTP-1B. PE also altered cell shape but this was unaffected by MKP-1. There was also no clear effect of MKP-1 on the organization of the contractile apparatus into sarcomeric structures in the presence of 10 microM PE. We conclude that the transcriptional responses accompanying cardiac myocyte hypertrophy are dependent on an MKP-1-sensitive step, presumably the activation of one or members of the MAPK family, but that cell size, shape and myofibrillar organization are much less sensitive to inhibition by MKP-1.

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Selected References

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  1. Abdellatif M., MacLellan W. R., Schneider M. D. p21 Ras as a governor of global gene expression. J Biol Chem. 1994 Jun 3;269(22):15423–15426. [PubMed] [Google Scholar]
  2. Ahn N. G., Seger R., Krebs E. G. The mitogen-activated protein kinase activator. Curr Opin Cell Biol. 1992 Dec;4(6):992–999. doi: 10.1016/0955-0674(92)90131-u. [DOI] [PubMed] [Google Scholar]
  3. Alessi D. R., Gomez N., Moorhead G., Lewis T., Keyse S. M., Cohen P. Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines. Curr Biol. 1995 Mar 1;5(3):283–295. doi: 10.1016/s0960-9822(95)00059-5. [DOI] [PubMed] [Google Scholar]
  4. Allo S. N., McDermott P. J., Carl L. L., Morgan H. E. Phorbol ester stimulation of protein kinase C activity and ribosomal DNA transcription. Role in hypertrophic growth of cultured cardiomyocytes. J Biol Chem. 1991 Nov 15;266(32):22003–22009. [PubMed] [Google Scholar]
  5. Blumer K. J., Johnson G. L. Diversity in function and regulation of MAP kinase pathways. Trends Biochem Sci. 1994 Jun;19(6):236–240. doi: 10.1016/0968-0004(94)90147-3. [DOI] [PubMed] [Google Scholar]
  6. Bogoyevitch M. A., Andersson M. B., Gillespie-Brown J., Clerk A., Glennon P. E., Fuller S. J., Sugden P. H. Adrenergic receptor stimulation of the mitogen-activated protein kinase cascade and cardiac hypertrophy. Biochem J. 1996 Feb 15;314(Pt 1):115–121. doi: 10.1042/bj3140115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bogoyevitch M. A., Gillespie-Brown J., Ketterman A. J., Fuller S. J., Ben-Levy R., Ashworth A., Marshall C. J., Sugden P. H. Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion. Circ Res. 1996 Aug;79(2):162–173. doi: 10.1161/01.res.79.2.162. [DOI] [PubMed] [Google Scholar]
  8. Bogoyevitch M. A., Glennon P. E., Andersson M. B., Clerk A., Lazou A., Marshall C. J., Parker P. J., Sugden P. H. Endothelin-1 and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signaling pathways leading to myocyte hypertrophy. J Biol Chem. 1994 Jan 14;269(2):1110–1119. [PubMed] [Google Scholar]
  9. Bogoyevitch M. A., Glennon P. E., Andersson M. B., Lazou A., Marshall C. J., Sugden P. H. Acidic fibroblast growth factor or endothelin-1 stimulate the MAP kinase cascade in cardiac myocytes. Biochem Soc Trans. 1993 Nov;21(4):358S–358S. doi: 10.1042/bst021358s. [DOI] [PubMed] [Google Scholar]
  10. Bogoyevitch M. A., Glennon P. E., Sugden P. H. Endothelin-1, phorbol esters and phenylephrine stimulate MAP kinase activities in ventricular cardiomyocytes. FEBS Lett. 1993 Feb 15;317(3):271–275. doi: 10.1016/0014-5793(93)81291-7. [DOI] [PubMed] [Google Scholar]
  11. Bogoyevitch M. A., Ketterman A. J., Sugden P. H. Cellular stresses differentially activate c-Jun N-terminal protein kinases and extracellular signal-regulated protein kinases in cultured ventricular myocytes. J Biol Chem. 1995 Dec 15;270(50):29710–29717. doi: 10.1074/jbc.270.50.29710. [DOI] [PubMed] [Google Scholar]
  12. Bogoyevitch M. A., Parker P. J., Sugden P. H. Characterization of protein kinase C isotype expression in adult rat heart. Protein kinase C-epsilon is a major isotype present, and it is activated by phorbol esters, epinephrine, and endothelin. Circ Res. 1993 Apr;72(4):757–767. doi: 10.1161/01.res.72.4.757. [DOI] [PubMed] [Google Scholar]
  13. Brand T., MacLellan W. R., Schneider M. D. A dominant-negative receptor for type beta transforming growth factors created by deletion of the kinase domain. J Biol Chem. 1993 Jun 5;268(16):11500–11503. [PubMed] [Google Scholar]
  14. Brondello J. M., McKenzie F. R., Sun H., Tonks N. K., Pouysségur J. Constitutive MAP kinase phosphatase (MKP-1) expression blocks G1 specific gene transcription and S-phase entry in fibroblasts. Oncogene. 1995 May 18;10(10):1895–1904. [PubMed] [Google Scholar]
  15. Charbonneau H., Tonks N. K. 1002 protein phosphatases? Annu Rev Cell Biol. 1992;8:463–493. doi: 10.1146/annurev.cb.08.110192.002335. [DOI] [PubMed] [Google Scholar]
  16. Charles C. H., Abler A. S., Lau L. F. cDNA sequence of a growth factor-inducible immediate early gene and characterization of its encoded protein. Oncogene. 1992 Jan;7(1):187–190. [PubMed] [Google Scholar]
  17. Chen R. H., Sarnecki C., Blenis J. Nuclear localization and regulation of erk- and rsk-encoded protein kinases. Mol Cell Biol. 1992 Mar;12(3):915–927. doi: 10.1128/mcb.12.3.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cherrington J. M., Mocarski E. S. Human cytomegalovirus ie1 transactivates the alpha promoter-enhancer via an 18-base-pair repeat element. J Virol. 1989 Mar;63(3):1435–1440. doi: 10.1128/jvi.63.3.1435-1440.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Chu Y., Solski P. A., Khosravi-Far R., Der C. J., Kelly K. The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation. J Biol Chem. 1996 Mar 15;271(11):6497–6501. doi: 10.1074/jbc.271.11.6497. [DOI] [PubMed] [Google Scholar]
  20. Clerk A., Bogoyevitch M. A., Anderson M. B., Sugden P. H. Differential activation of protein kinase C isoforms by endothelin-1 and phenylephrine and subsequent stimulation of p42 and p44 mitogen-activated protein kinases in ventricular myocytes cultured from neonatal rat hearts. J Biol Chem. 1994 Dec 30;269(52):32848–32857. [PubMed] [Google Scholar]
  21. Clerk A., Bogoyevitch M. A., Fuller S. J., Lazou A., Parker P. J., Sugden P. H. Expression of protein kinase C isoforms during cardiac ventricular development. Am J Physiol. 1995 Sep;269(3 Pt 2):H1087–H1097. doi: 10.1152/ajpheart.1995.269.3.H1087. [DOI] [PubMed] [Google Scholar]
  22. Clerk A., Gillespie-Brown J., Fuller S. J., Sugden P. H. Stimulation of phosphatidylinositol hydrolysis, protein kinase C translocation, and mitogen-activated protein kinase activity by bradykinin in rat ventricular myocytes: dissociation from the hypertrophic response. Biochem J. 1996 Jul 1;317(Pt 1):109–118. doi: 10.1042/bj3170109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Cobb M. H., Goldsmith E. J. How MAP kinases are regulated. J Biol Chem. 1995 Jun 23;270(25):14843–14846. doi: 10.1074/jbc.270.25.14843. [DOI] [PubMed] [Google Scholar]
  24. Davis R. J. The mitogen-activated protein kinase signal transduction pathway. J Biol Chem. 1993 Jul 15;268(20):14553–14556. [PubMed] [Google Scholar]
  25. Decock J. B., Gillespie-Brown J., Parker P. J., Sugden P. H., Fuller S. J. Classical, novel and atypical isoforms of PKC stimulate ANF- and TRE/AP-1-regulated-promoter activity in ventricular cardiomyocytes. FEBS Lett. 1994 Dec 19;356(2-3):275–278. doi: 10.1016/0014-5793(94)01283-0. [DOI] [PubMed] [Google Scholar]
  26. Dent P., Haser W., Haystead T. A., Vincent L. A., Roberts T. M., Sturgill T. W. Activation of mitogen-activated protein kinase kinase by v-Raf in NIH 3T3 cells and in vitro. Science. 1992 Sep 4;257(5075):1404–1407. doi: 10.1126/science.1326789. [DOI] [PubMed] [Google Scholar]
  27. Duff J. L., Monia B. P., Berk B. C. Mitogen-activated protein (MAP) kinase is regulated by the MAP kinase phosphatase (MKP-1) in vascular smooth muscle cells. Effect of actinomycin D and antisense oligonucleotides. J Biol Chem. 1995 Mar 31;270(13):7161–7166. doi: 10.1074/jbc.270.13.7161. [DOI] [PubMed] [Google Scholar]
  28. Dunnmon P. M., Iwaki K., Henderson S. A., Sen A., Chien K. R. Phorbol esters induce immediate-early genes and activate cardiac gene transcription in neonatal rat myocardial cells. J Mol Cell Cardiol. 1990 Aug;22(8):901–910. doi: 10.1016/0022-2828(90)90121-h. [DOI] [PubMed] [Google Scholar]
  29. Ferguson J. J. American College of Cardiology 45th Annual Scientific Session, Orlando, Florida, March 24 to 27, 1996. Circulation. 1996 Jul 1;94(1):1–5. doi: 10.1161/01.cir.94.1.1. [DOI] [PubMed] [Google Scholar]
  30. Fire A., Harrison S. W., Dixon D. A modular set of lacZ fusion vectors for studying gene expression in Caenorhabditis elegans. Gene. 1990 Sep 14;93(2):189–198. doi: 10.1016/0378-1119(90)90224-f. [DOI] [PubMed] [Google Scholar]
  31. Fuller S. J., Sugden P. H. Protein synthesis in rat cardiac myocytes is stimulated at the level of translation by phorbol esters. FEBS Lett. 1989 Apr 24;247(2):209–212. doi: 10.1016/0014-5793(89)81336-5. [DOI] [PubMed] [Google Scholar]
  32. Gillespie-Brown J., Fuller S. J., Bogoyevitch M. A., Cowley S., Sugden P. H. The mitogen-activated protein kinase kinase MEK1 stimulates a pattern of gene expression typical of the hypertrophic phenotype in rat ventricular cardiomyocytes. J Biol Chem. 1995 Nov 24;270(47):28092–28096. doi: 10.1074/jbc.270.47.28092. [DOI] [PubMed] [Google Scholar]
  33. Glennon P. E., Kaddoura S., Sale E. M., Sale G. J., Fuller S. J., Sugden P. H. Depletion of mitogen-activated protein kinase using an antisense oligodeoxynucleotide approach downregulates the phenylephrine-induced hypertrophic response in rat cardiac myocytes. Circ Res. 1996 Jun;78(6):954–961. doi: 10.1161/01.res.78.6.954. [DOI] [PubMed] [Google Scholar]
  34. Henderson S. A., Spencer M., Sen A., Kumar C., Siddiqui M. A., Chien K. R. Structure, organization, and expression of the rat cardiac myosin light chain-2 gene. Identification of a 250-base pair fragment which confers cardiac-specific expression. J Biol Chem. 1989 Oct 25;264(30):18142–18148. [PubMed] [Google Scholar]
  35. Henrich C. J., Simpson P. C. Differential acute and chronic response of protein kinase C in cultured neonatal rat heart myocytes to alpha 1-adrenergic and phorbol ester stimulation. J Mol Cell Cardiol. 1988 Dec;20(12):1081–1085. doi: 10.1016/0022-2828(88)90588-3. [DOI] [PubMed] [Google Scholar]
  36. Howe L. R., Leevers S. J., Gómez N., Nakielny S., Cohen P., Marshall C. J. Activation of the MAP kinase pathway by the protein kinase raf. Cell. 1992 Oct 16;71(2):335–342. doi: 10.1016/0092-8674(92)90361-f. [DOI] [PubMed] [Google Scholar]
  37. Ito A., Satoh T., Kaziro Y., Itoh H. G protein beta gamma subunit activates Ras, Raf, and MAP kinase in HEK 293 cells. FEBS Lett. 1995 Jul 10;368(1):183–187. doi: 10.1016/0014-5793(95)00643-n. [DOI] [PubMed] [Google Scholar]
  38. Iwaki K., Sukhatme V. P., Shubeita H. E., Chien K. R. Alpha- and beta-adrenergic stimulation induces distinct patterns of immediate early gene expression in neonatal rat myocardial cells. fos/jun expression is associated with sarcomere assembly; Egr-1 induction is primarily an alpha 1-mediated response. J Biol Chem. 1990 Aug 15;265(23):13809–13817. [PubMed] [Google Scholar]
  39. Kaku T., Lakatta E., Filburn C. Alpha-adrenergic regulation of phosphoinositide metabolism and protein kinase C in isolated cardiac myocytes. Am J Physiol. 1991 Mar;260(3 Pt 1):C635–C642. doi: 10.1152/ajpcell.1991.260.3.C635. [DOI] [PubMed] [Google Scholar]
  40. Kariya K., Karns L. R., Simpson P. C. Expression of a constitutively activated mutant of the beta-isozyme of protein kinase C in cardiac myocytes stimulates the promoter of the beta-myosin heavy chain isogene. J Biol Chem. 1991 Jun 5;266(16):10023–10026. [PubMed] [Google Scholar]
  41. Knowlton K. U., Baracchini E., Ross R. S., Harris A. N., Henderson S. A., Evans S. M., Glembotski C. C., Chien K. R. Co-regulation of the atrial natriuretic factor and cardiac myosin light chain-2 genes during alpha-adrenergic stimulation of neonatal rat ventricular cells. Identification of cis sequences within an embryonic and a constitutive contractile protein gene which mediate inducible expression. J Biol Chem. 1991 Apr 25;266(12):7759–7768. [PubMed] [Google Scholar]
  42. Koch W. J., Hawes B. E., Allen L. F., Lefkowitz R. J. Direct evidence that Gi-coupled receptor stimulation of mitogen-activated protein kinase is mediated by G beta gamma activation of p21ras. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12706–12710. doi: 10.1073/pnas.91.26.12706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Kyriakis J. M., App H., Zhang X. F., Banerjee P., Brautigan D. L., Rapp U. R., Avruch J. Raf-1 activates MAP kinase-kinase. Nature. 1992 Jul 30;358(6385):417–421. doi: 10.1038/358417a0. [DOI] [PubMed] [Google Scholar]
  44. LaMorte V. J., Thorburn J., Absher D., Spiegel A., Brown J. H., Chien K. R., Feramisco J. R., Knowlton K. U. Gq- and ras-dependent pathways mediate hypertrophy of neonatal rat ventricular myocytes following alpha 1-adrenergic stimulation. J Biol Chem. 1994 May 6;269(18):13490–13496. [PubMed] [Google Scholar]
  45. Lazou A., Bogoyevitch M. A., Clerk A., Fuller S. J., Marshall C J., Sugden P. H. Regulation of mitogen-activated protein kinase cascade in adult rat heart preparations in vitro. Circ Res. 1994 Nov;75(5):932–941. doi: 10.1161/01.res.75.5.932. [DOI] [PubMed] [Google Scholar]
  46. Lee H. R., Henderson S. A., Reynolds R., Dunnmon P., Yuan D., Chien K. R. Alpha 1-adrenergic stimulation of cardiac gene transcription in neonatal rat myocardial cells. Effects on myosin light chain-2 gene expression. J Biol Chem. 1988 May 25;263(15):7352–7358. [PubMed] [Google Scholar]
  47. Lev S., Moreno H., Martinez R., Canoll P., Peles E., Musacchio J. M., Plowman G. D., Rudy B., Schlessinger J. Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion channel and MAP kinase functions. Nature. 1995 Aug 31;376(6543):737–745. doi: 10.1038/376737a0. [DOI] [PubMed] [Google Scholar]
  48. Liu Y., Gorospe M., Yang C., Holbrook N. J. Role of mitogen-activated protein kinase phosphatase during the cellular response to genotoxic stress. Inhibition of c-Jun N-terminal kinase activity and AP-1-dependent gene activation. J Biol Chem. 1995 Apr 14;270(15):8377–8380. doi: 10.1074/jbc.270.15.8377. [DOI] [PubMed] [Google Scholar]
  49. Long C. S., Ordahl C. P., Simpson P. C. Alpha 1-adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells. J Clin Invest. 1989 Mar;83(3):1078–1082. doi: 10.1172/JCI113951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. MacLellan W. R., Lee T. C., Schwartz R. J., Schneider M. D. Transforming growth factor-beta response elements of the skeletal alpha-actin gene. Combinatorial action of serum response factor, YY1, and the SV40 enhancer-binding protein, TEF-1. J Biol Chem. 1994 Jun 17;269(24):16754–16760. [PubMed] [Google Scholar]
  51. Marshall C. J. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr Opin Genet Dev. 1994 Feb;4(1):82–89. doi: 10.1016/0959-437x(94)90095-7. [DOI] [PubMed] [Google Scholar]
  52. Marshall C. J. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell. 1995 Jan 27;80(2):179–185. doi: 10.1016/0092-8674(95)90401-8. [DOI] [PubMed] [Google Scholar]
  53. McCormick F. Signal transduction. How receptors turn Ras on. Nature. 1993 May 6;363(6424):15–16. doi: 10.1038/363015a0. [DOI] [PubMed] [Google Scholar]
  54. McDermott P. J., Morgan H. E. Contraction modulates the capacity for protein synthesis during growth of neonatal heart cells in culture. Circ Res. 1989 Mar;64(3):542–553. doi: 10.1161/01.res.64.3.542. [DOI] [PubMed] [Google Scholar]
  55. McDermott P. J., Rothblum L. I., Smith S. D., Morgan H. E. Accelerated rates of ribosomal RNA synthesis during growth of contracting heart cells in culture. J Biol Chem. 1989 Oct 25;264(30):18220–18227. [PubMed] [Google Scholar]
  56. Minshull J., Sun H., Tonks N. K., Murray A. W. A MAP kinase-dependent spindle assembly checkpoint in Xenopus egg extracts. Cell. 1994 Nov 4;79(3):475–486. doi: 10.1016/0092-8674(94)90256-9. [DOI] [PubMed] [Google Scholar]
  57. Mourey R. J., Vega Q. C., Campbell J. S., Wenderoth M. P., Hauschka S. D., Krebs E. G., Dixon J. E. A novel cytoplasmic dual specificity protein tyrosine phosphatase implicated in muscle and neuronal differentiation. J Biol Chem. 1996 Feb 16;271(7):3795–3802. doi: 10.1074/jbc.271.7.3795. [DOI] [PubMed] [Google Scholar]
  58. Parker T. G., Chow K. L., Schwartz R. J., Schneider M. D. Positive and negative control of the skeletal alpha-actin promoter in cardiac muscle. A proximal serum response element is sufficient for induction by basic fibroblast growth factor (FGF) but not for inhibition by acidic FGF. J Biol Chem. 1992 Feb 15;267(5):3343–3350. [PubMed] [Google Scholar]
  59. Post G. R., Goldstein D., Thuerauf D. J., Glembotski C. C., Brown J. H. Dissociation of p44 and p42 mitogen-activated protein kinase activation from receptor-induced hypertrophy in neonatal rat ventricular myocytes. J Biol Chem. 1996 Apr 5;271(14):8452–8457. doi: 10.1074/jbc.271.14.8452. [DOI] [PubMed] [Google Scholar]
  60. Robbins D. J., Zhen E., Cheng M., Xu S., Ebert D., Cobb M. H. MAP kinases ERK1 and ERK2: pleiotropic enzymes in a ubiquitous signaling network. Adv Cancer Res. 1994;63:93–116. doi: 10.1016/s0065-230x(08)60399-1. [DOI] [PubMed] [Google Scholar]
  61. Rohan P. J., Davis P., Moskaluk C. A., Kearns M., Krutzsch H., Siebenlist U., Kelly K. PAC-1: a mitogen-induced nuclear protein tyrosine phosphatase. Science. 1993 Mar 19;259(5102):1763–1766. doi: 10.1126/science.7681221. [DOI] [PubMed] [Google Scholar]
  62. 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]
  63. Sadoshima J., Qiu Z., Morgan J. P., Izumo S. Angiotensin II and other hypertrophic stimuli mediated by G protein-coupled receptors activate tyrosine kinase, mitogen-activated protein kinase, and 90-kD S6 kinase in cardiac myocytes. The critical role of Ca(2+)-dependent signaling. Circ Res. 1995 Jan;76(1):1–15. doi: 10.1161/01.res.76.1.1. [DOI] [PubMed] [Google Scholar]
  64. Seger R., Krebs E. G. The MAPK signaling cascade. FASEB J. 1995 Jun;9(9):726–735. [PubMed] [Google Scholar]
  65. Sei C. A., Irons C. E., Sprenkle A. B., McDonough P. M., Brown J. H., Glembotski C. C. The alpha-adrenergic stimulation of atrial natriuretic factor expression in cardiac myocytes requires calcium influx, protein kinase C, and calmodulin-regulated pathways. J Biol Chem. 1991 Aug 25;266(24):15910–15916. [PubMed] [Google Scholar]
  66. Seth A., Gonzalez F. A., Gupta S., Raden D. L., Davis R. J. Signal transduction within the nucleus by mitogen-activated protein kinase. J Biol Chem. 1992 Dec 5;267(34):24796–24804. [PubMed] [Google Scholar]
  67. Shubeita H. E., Martinson E. A., Van Bilsen M., Chien K. R., Brown J. H. Transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase C in neonatal rat ventricular myocytes. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1305–1309. doi: 10.1073/pnas.89.4.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Shubeita H. E., Martinson E. A., Van Bilsen M., Chien K. R., Brown J. H. Transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase C in neonatal rat ventricular myocytes. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1305–1309. doi: 10.1073/pnas.89.4.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Shubeita H. E., McDonough P. M., Harris A. N., Knowlton K. U., Glembotski C. C., Brown J. H., Chien K. R. Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. A paracrine mechanism for myocardial cell hypertrophy. J Biol Chem. 1990 Nov 25;265(33):20555–20562. [PubMed] [Google Scholar]
  70. Sun H., Charles C. H., Lau L. F., Tonks N. K. MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo. Cell. 1993 Nov 5;75(3):487–493. doi: 10.1016/0092-8674(93)90383-2. [DOI] [PubMed] [Google Scholar]
  71. Sun H., Tonks N. K., Bar-Sagi D. Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1. Science. 1994 Oct 14;266(5183):285–288. doi: 10.1126/science.7939666. [DOI] [PubMed] [Google Scholar]
  72. Thorburn A., Thorburn J., Chen S. Y., Powers S., Shubeita H. E., Feramisco J. R., Chien K. R. HRas-dependent pathways can activate morphological and genetic markers of cardiac muscle cell hypertrophy. J Biol Chem. 1993 Jan 25;268(3):2244–2249. [PubMed] [Google Scholar]
  73. Thorburn J., Carlson M., Mansour S. J., Chien K. R., Ahn N. G., Thorburn A. Inhibition of a signaling pathway in cardiac muscle cells by active mitogen-activated protein kinase kinase. Mol Biol Cell. 1995 Nov;6(11):1479–1490. doi: 10.1091/mbc.6.11.1479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Thorburn J., Frost J. A., Thorburn A. Mitogen-activated protein kinases mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy. J Cell Biol. 1994 Sep;126(6):1565–1572. doi: 10.1083/jcb.126.6.1565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Thorburn J., McMahon M., Thorburn A. Raf-1 kinase activity is necessary and sufficient for gene expression changes but not sufficient for cellular morphology changes associated with cardiac myocyte hypertrophy. J Biol Chem. 1994 Dec 2;269(48):30580–30586. [PubMed] [Google Scholar]
  76. Ward Y., Gupta S., Jensen P., Wartmann M., Davis R. J., Kelly K. Control of MAP kinase activation by the mitogen-induced threonine/tyrosine phosphatase PAC1. Nature. 1994 Feb 17;367(6464):651–654. doi: 10.1038/367651a0. [DOI] [PubMed] [Google Scholar]
  77. Waspe L. E., Ordahl C. P., Simpson P. C. The cardiac beta-myosin heavy chain isogene is induced selectively in alpha 1-adrenergic receptor-stimulated hypertrophy of cultured rat heart myocytes. J Clin Invest. 1990 Apr;85(4):1206–1214. doi: 10.1172/JCI114554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Yamazaki T., Komuro I., Kudoh S., Zou Y., Shiojima I., Mizuno T., Takano H., Hiroi Y., Ueki K., Tobe K. Mechanical stress activates protein kinase cascade of phosphorylation in neonatal rat cardiac myocytes. J Clin Invest. 1995 Jul;96(1):438–446. doi: 10.1172/JCI118054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Yamazaki T., Tobe K., Hoh E., Maemura K., Kaida T., Komuro I., Tamemoto H., Kadowaki T., Nagai R., Yazaki Y. Mechanical loading activates mitogen-activated protein kinase and S6 peptide kinase in cultured rat cardiac myocytes. J Biol Chem. 1993 Jun 5;268(16):12069–12076. [PubMed] [Google Scholar]
  80. de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]

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