CD4 ligation induces activation of protein kinase C zeta and phosphoinositide-dependent-protein kinase-1, two kinases required for down-regulation of LFA-1-mediated adhesion |
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Authors: | Trucy Maÿlis Barbat Christiane Fischer Alain Mazerolles Fabienne |
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Institution: | a INSERM, U768, 75015, Site Necker, 147 rue de sevres Paris, F-75015 Paris, France b Université Paris-Descartes, Faculté de médecine René Descartes, Paris, France c AP HP, Hospital Necker, Paris, France |
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Abstract: | We previously showed that CD4 binding induced a down-regulation of LFA-1-dependent-antigen-independent adhesion of T and B lymphocytes in a phosphatidylinositol-3-kinase (PI3K)-dependent manner. We now show in A201-CD4 (+) T cell lines, that anti-CD4 Ab increases activation of phosphoinositide-dependent-protein-kinase 1 (PDK1) or PKC zeta, two main effectors down-stream from PI3K. CD4 binding also increases interactions between PI3K and activated PKCzeta and PDK1. Both events are dependent on CD4/p56Lck association, since they are not detected when p56Lck is unable to bind a truncated form of CD4 in transfected T cell lines. We also show using antisense oligonucleotides that both kinases are necessary for down-regulating LFA-1-dependent adhesion induced by CD4 signalling. We also suggest a role of PDK1 in the recruitment of the phosphatase SHP-2 in a multiprotein complex induced by anti-CD4 Ab. This study thus provides further insights into the mechanism underlying the CD4 triggered regulation of LFA-1-mediated adhesion. |
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Keywords: | Activation Adhesion CD4 Kinases PI3K |
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