Posttranslational modifications on protein kinase c isozymes. Effects of epinephrine and phorbol esters

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• 作者：Martha Robles-Flores ; Lennon Melé ; ndez ; Wendy Garcí ; a ; Guillermo Mendoza-Herná ; ndez ; Tukiet T. Lam ; Cristina Castañ ; eda-Patlá ; n ; Hé ; ctor Gonzá ; lez-Aguilar
• 关键词：PKC ; Posttranslational modification ; O-GlcNAc glycosylation ; Tyrosine nitration ; Tyrosine phosphorylation ; Protein phosphorylation
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2008
• 期刊代码：20_01674889
• 类别：bio
• 出版时间：May 2008
• 卷：1783
• 期：5
• 页码：695-712
• 文件大小：3316 K

摘要

The posttranslational modifications induced on PKC isozymes as result of their activation were investigated. Reciprocal immunoprecipitations followed by Western blot analysis demonstrated that all PKC isozymes expressed in rat hepatocytes are modified by tyrosine nitration and tyrosine phosphorylation in different ways upon exposure of cells to a direct PKC activator (TPA), or to an extracellular ligand known to activate PKC-dependent pathways (epinephrine). Our data demonstrate for the first time that all PKC isozymes are also dynamically modified by O-linked β-N-acetylglucosamine (O-GlcNAc); the presence of this modification was confirmed in part by FT-ICR mass spectrometry analysis. Interestingly, the O-GlcNAc modified Ser or Thr were mapped at similar positions in several PKC isozymes. The biochemical meaning of these posttranslational modifications was investigated for PKC alpha and delta. It was found that the PKC phosphorylation status of both isozymes in tyrosine and serine residues seems to regulate directly the enzyme activity since catalytic inactivation correlate with dephosphorylation of Ser at the C-terminus autophosphorylation sites of each PKC isozyme, and with an increase in the level of tyrosine phosphorylation. Whereas none of the other posttranslational modifications showed per se a direct effect in PKC delta activity, increased tyrosine nitration and O-GlcNAc modifications correlate negatively with PKCom/scidirimg/entities/204e.gif" alt="greek small letter alpha" title="greek small letter alpha" border="0"> activity.