Protein kinase D is sufficient to suppress EGF-induced c-Jun Ser 63 phosphorylation.
Phosphorylation of c-Jun at Ser 63/73 by the c-Jun N-terminal kinase (JNK) potentiates the transactivation function of c-Jun. Protein kinase D (PKD), a downstream effector of protein kinase C (PKC), has been implicated in the attenuation of epidermal growth factor (EGF)-induced activation of JNK. In order to determine whether activated PKD is sufficient to modulate the EGF-JNK-c-Jun pathway, we have developed a cellular model system, utilizing human embryonic kidney cells (HEK 293), in which stably transfected, constitutively active or kinase dead mutants of PKD can be inducibly expressed by the insect hormone, ecdysone. Induced expression of constitutively active, but not kinase dead PKD, suppressed EGF stimulated c-Jun phosphorylation at Ser 63, demonstrating that activated PKD is sufficient to suppress c-Jun phosphorylation. This is the first demonstration that PKD modulates phosphorylation of the proto-oncogene c-Jun at a site critical for its ability to mediate cell proliferation and differentiation.
Hurd
C
C
Department of Medicine, University of California, Los Angeles, California 90095, USA.
Rozengurt
E
E
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D004440:Ecdysone / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D014162:Transfection
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D004440:Ecdysone; D012694:Serine; D004815:Epidermal Growth Factor; C089212:protein kinase D; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases