Nerve growth factor-activated protein kinase N modulates the cAMP-dependent protein kinase.
Protein kinase N (PKN) is a serine/threonine protein kinase rapidly activated by nerve growth factor (NGF) and other agents in various cell lines. The possible involvement of PKN in the multiple pathways of the NGF mechanism of action was previously established through the use of purine analogs, some of which are apparently specific inhibitors of this kinase. Since a PKN-like activity is modulated in several cell lines by cAMP analogs and this activation requires the activity of cAMP-dependent protein kinase, the aim of the present work is to investigate possible interactions between PKN and C-PKA. Pre-incubation of the two kinases in the presence of ATP leads to potentiated phosphorylation of histone HF1, Kemptide (a substrate for C-PKA, but not for PKN), and several additional substrates. This augmented phosphorylating activity is insensitive to 6-thioguanine (an inhibitor for PKN, but not for C-PKA) and is suppressed both by the Walsh inhibitor and by the regulatory subunit of PKA. PKN-pretreated C-PKA shows a significant decrease in Km for Kemptide and a substantial increase in Vmax. C-PKA and PKN are widely expressed enzymes and the possibility of PKN-dependent modulation of PKA in intact cells would therefore have biological implications for signal transduction mechanisms.
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Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York.
Greene
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D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D009414:Nerve Growth Factors / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D016716:PC12 Cells / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013866:Thioguanine / Q000494:pharmacology
D009414:Nerve Growth Factors; D009842:Oligopeptides; C037642:kemptide; D000242:Cyclic AMP; D011494:Protein Kinases; C061570:protein kinase N; D011493:Protein Kinase C; D013866:Thioguanine