G Baier

Publications (2)11.15 Total impact

• Article: Differential requirements for ERK1/2 and P38 MAPK activation by thrombin in T cells. Role of P59Fyn and PKCepsilon.

  L Maulon, B Mari, C Bertolotto, J E Ricci, F Luciano, N Belhacene, M Deckert, G Baier, P Auberger
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  ABSTRACT: Activation of the mitogen-activated protein kinase (MAPK) cascade is a well documented mechanism for the G-protein-coupled receptors. Here, we have analysed the requirements for ERKs and p38 MAPK activation by thrombin in Jurkat T cells. We show that thrombin-mediated ERKs activation requires both PTK and PKC activities, whereas p38 MAPK activation is dependent only on PTKs. Thrombin-induced ERK and p38 MAPK activation was more pronounced in p56Lck deficient cells indicating that this PTK exerts a negative control on MAPK activity. Accordingly, overexpression of p50 Csk a kinase that inactivates p56Lck induced constitutive activation of ERKs. Requirement for a Src kinase was evidenced by expression of a constitutively active form of p59Fyn in Jurkat cells. Besides its effect on tyrosine phosphorylation events, thrombin also triggered a rapid and robust redistribution of PKCepsilon and delta from the cytosol to the membrane. Expression of constitutively active and dominant negative PKCepsilon demonstrates the pivotal role of this PKC isoform in ERKs activation by thrombin. These data are consistent with a model where thrombin induces ERK activation via both PKC-dependent and independent pathways, whereas p38 MAPK activation requires only PTKs. The PKC-independent pathway requires Src kinases other than p56Lck more likely p59Fyn, while the PKC-dependent mechanism depends on PKCepsilon
  Oncogene 05/2001; 20(16):1964-72. · 6.37 Impact Factor
• Article: Protein kinase C theta and epsilon promote T-cell survival by a rsk-dependent phosphorylation and inactivation of BAD.

  C Bertolotto, L Maulon, N Filippa, G Baier, P Auberger
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  ABSTRACT: Both MAPK and protein kinase C (PKC) signaling pathways promote cell survival and protect against cell death. Here, we show that 12-O-tetradecanoylphorbol-13-acetate (TPA) prevents Fas-induced apoptosis in T lymphocytes. The effect of TPA was specifically abolished by the PKC inhibitor GF109203X and by dominant negative PKCtheta, PKCepsilon, and PKCalpha, suggesting that novel and conventional PKC isoforms mediate phorbol ester action. Moreover, TPA stimulated phosphorylation of BAD at serine 112, an effect abrogated by GF109203X but not by the MEK inhibitor PD98059. Expression of constitutively active PKC increased the phosphorylation of BAD at serine 112 but not at serine 136. Additionally, Fas-mediated cell death was enhanced by overexpression of a catalytically inactive form of p90Rsk (Rsk2-KN). Finally, Rsk2-KN abolished the protective effect of constitutively active PKC and totally blocked phosphorylation of BAD on serine 112. Thus, novel PKCtheta and PKCepsilon rescue T lymphocytes from Fas-mediated apoptosis via a p90Rsk-dependent phosphorylation and inactivation of BAD.
  Journal of Biological Chemistry 12/2000; 275(47):37246-50. · 4.77 Impact Factor