Abstract
Protein kinase C (PKC) is a signal transducing enzyme, that has been related to the regulation of proliferative and morphogenetic processes in many eukaryotic systems. The yeast to mycelium transition in Sporothrix schenckii involves both morphogenesis and proliferation and has been reported by us to be stimulated by calcium ions but can occur in the absence of this cation. The work reported here suggests the involvement of PKC in the induction of the yeast to mycelium transition in S. schenkii in the absence of extracellular calcium ions. Phorbol-12-myristate-13-acetate (PMA), a tumor promoting agent and PKC activator was found to stimulate germ tube formation and germ tube growth by yeast cells induced to undergo transition to the mycelium form in a concentration dependent manner with an optimal stimulatory concentration of 2 µM. This same PMA concentration had a stimulatory effect on DNA and RNA synthesis in cells induced to undergo the yeast to mycelium transition and was found to inhibit cell duplication and bud formation in yeast cells induced to re-enter the budding cycle. Polymyxin B, an inhibitor of PKC, inhibited germ tube formation by yeast cells at concentrations of 50 and 100 µM, at all time intervals tested. This inhibition could be overcome if PMA 2 µM or calcium 1 mM were added to the medium, suggesting that the inhibition obtained in the presence of this antibiotic was due to an inhibition of PKC. These results support the involvement of PKC in the control of the dimorphic expression in S. schenckii. Other PKC inhibitors tested, H-7 and staurosporine gave unexpected results, probably because of their lack of specificity and the fact that they inhibit other protein kinases.
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References
S. Betancourt, L.J.Torres-Bauzá and N. Rodriguez-del Valle, Molecular and cellular events during the yeast to mycelium transition in Sporothrix schenckii, Sabouraudia ,23: 207 (1985).
S. Resto and N. Rodriguez-del Valle, Yeast cell cycle of Sporothrix schenckii , J. Vet. Med. Mycol. 26: 13 (1988).
C. Metcalfe, J.P.Moore, G.A.Smith and T.R. Hesketh, Calcium and cell proliferation, Br. Med. Bull. 42: 405 (1986).
M. Poenie and R.A. Steinhardt, The dynamics of [Ca2+] during mitosis, Calcium and Cell Function 1: 133 (1987).
R.B. Silver, Calcium and cellular clocks orchestrate cell division, Ann. N.Y. Acad. Sci. 582: 207 (1990).
S. Serrano and N. Rodriguez-del Valle, Calcium uptake and efflux during the yeast to mycelium transition in Sporothrix schenckii, Mycopathol. 112: 1 (1990).
Y. Nishizuka, Studies and perspectives of protein kinase C, Science 233: 305 (1986).
Y. Nizishuka, The role of protein kinase C on cell surface signal transduction and tumor promotion, Nature 308: 693 (1984).
U. Kikawa, Y. Takai, Y. Tanaka, R. Mikaya and Y. Nishizuka, Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters, J. Cell Biol. 258: 11442 (1983).
G.J. Mazzei, N. Katoh and J.F. Kuo, Polymyxin B a more selective inhibitor for phospholipid sensitive Ca2+-dependent protein kinase than for calmodulin-sensitive Ca2+-dependent protein kinase, Biochem. Biophys. Res. Commun. 109: 1129 (1982).
H. Hidaka, M. Inagaki, S. Kawamoto and Y. Sasaki, Isoquinoline sulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C, Biochem. 23,5036 (1984).
P.D. Davis, C.H. Hill, E. Keech, G. Lawton, J.S. Nixon, A.D. Sedgwick, J. Wadsworth, D. Westmacott and S.E. Wilkinson, Potent selective inhibitors of protein kinase C, FEBS Lett. 259: 61 (1989).
J. Hatzfeld, DNA labeling and its assay in yeast, Biochim. Biophys. Acta 229: 34 (1973)
E. Huberman, C. Heckman and R.Langenbach, Stimulation of differentiated functions in human melanoma cells by tumor-promoting agents and dimethylsulfoxide, Cancer Res. 39: 2618 (1979).
E. Huberman and M.F. Callahan, Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents, Proc. Natl. Acad. Sci. USA 76: 1293 (1979).
G. Rovera, T.G. O’Brien and L. Diamond, Induction of differentiation in human promyelocytic leukemia cells by tumor promoters, Science 204: 868 (1979).
P.L.Baron, M.J. Koretz, R.A. Carchman, J.M. Collins, A.S.Torkarz and G.A. Parker, Induction of the expression of differentiation-related antigens on human colon carcinoma cells by stimulating protein kinase C, Arch. Surg. 125: 344 (1990).
A.A. Farooqui, T. Farooqui, A.J. Yates and L.A. Horrocks, Regulation of protein kinase C activity by various lipids, Neurochem. Res. 13: 499 (1988).
R.C. Howe and H.R. MacDonald, Distinct effects of phorbol esters and exogenous diacylglycerols in the induction of murine thymocyte proliferation, J. Cell. Physiol. 151: 8 (1992).
G.J. Pasktan and C. S. Baxter, Specific stimulation by phorbol esters of the phosphorylation of histones H2B and 1.14 in murine lymphocytes, Cancer Res. 45: 667 (1985).
J.L. Tilly, and A.L. Johnson, Effect of a phorbol ester, a calcium ionophore and 3’,5’-adenosine monophosphate production on hen granulosa cell plasminogen activator activity, Endocrinol. 123: 1233 (1988).
E.G. Levin, K.R. Marotti and L. Santell, Protein kinase C and the stimulation of tissue plasminogen activator release from human endothelial cells, J. Biol. Chem. 264: 16030 (1989).
T. Haneda and P.J. Mc Dermott, Stimulation of ribosomal RNA synthesis during hyper-trophic growth of cultured heart cells by phorbol ester, Mol. Cell. Biochem. 104: 169 (1991).
S.N. Allo, P.J. Mc Dermott, L.L. Carl and H.E. Morgan, Phorbol ester stimulation of protein kinase C activity and ribosomal DNA transcription, J. Biol. Chem. 266: 22003 (1991).
D. Baranes and E. Razin, Protein kinase C regulates proliferation of mast cells and the expression of the mRNA of fos and jun proto-oncogenes during activation by IgE-Ag or calcium ionophore A23187, Blood 78: 2354 (1991).
M. Issandou and J. Darbon, Activation of protein kinase C by phorbol esters induces DNA synthesis and protein phosphorylation in glomerular mesangial cells, FEBS Lett. 281: 196 (1991).
J.M.Hebert, E. Seban and J.P. Maffraud, Characterization of specific binding sites for 3H-staurosporine on various protein kinases, Biochem. Biophys. Res. Commun. 171: 189 (1988).
CD. Smith, J.L. Glickman and K. Chang, The antiproliferative effects of staurosporine are not exclusively mediated by inhibition of protein kinase C, Biochem. Biophys. Res. Commun. 156: 1250 (1988).
A.G.H. Ederveen, S.E. Van Ernst-De Vries, J.J.H.H.M. De Pont and P.H.G.M. Willems, Dissimilar effects of the protein kinase C inhibitors, staurosporine and H-7 on cholecystokinininduced enzyme secretion from rabbit pancreatic acini, Eur. J. Biochem. 193: 291 (1990).
C.A.Bedoy and P.L.Mobley, Astrocyte morphology altered by 1-(5-isoquinolinylsulfonyl)-2 methyl piperazine (H-7) and other protein kinase inhibitors, Brain Res. 490: 243 (1989).
C. Schachtele, R. Seifert and H. Osswald, Stimulus-dependent inhibition of platelet aggregation by the protein kinase C inhibitor polymyxin B, H-7 and staurosporine, Biochem. Biophys. Res. Commun. 151: 542 (1988).
H.U. Keller, V. Niggli and A. Zimmermann, The protein kinase inhibitor H-7 activates human neutrophils: effect on shape, actin polymerization, fluid pinocytosis and locomotion, J. Cell Sci. 96: 99 (1990).
M. Watanabe, T. Tamura, M. Ohashi, N. Hirasawa, T. Ozeki, S. Tsurufuji, H. Fujiki and K. Ohuchi, Dual effects of staurosporine on arachidonic acid metabolism in rat peritoneal macrophages, Biochim. Biophys. Acta 1047: 141 (1990).
N. Rodriguez-del Valle, N. Debs-Elías and A. Alsina, Effects of caffeine, cyclic 3’,5’ adenosine monphosphate and cyclic 3’,5’ guanosine monophosphate in the development of the mycelium form of Sporothrix schenckii, Mycopathol 86, 29 (1984).
H. Kase, K. Iwahasi, S. Nakanishi, Y. Matsuda, K. Yamada, M. Takahashi, C. Murakata, A. Sato and M. Kaneko, K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide dependent protein kinases, Biochem. Biophys. Res. Commun. 142: 436 (1987).
T. Sako, A.I. Tauber, A.Y. Jeng, S.H. Yuspa and P.M. Blumberg, Contrasting actions of staurosporine a protein kinase C inhibitor on human neutrophils and primary mouse epidermal cells, Cancer Res. 48: 4646 (1988).
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Colon-Colon, W., Rodriguez-del Valle, N. (1993). Studies on Phase Transitions in Sporothrix Schenckii: Possible Involvement of Protein Kinase C. In: Vanden Bossche, H., Odds, F.C., Kerridge, D. (eds) Dimorphic Fungi in Biology and Medicine. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2834-0_19
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DOI: https://doi.org/10.1007/978-1-4615-2834-0_19
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