Pim-1 kinase enhances NFATc activity and neuroendocrine functions in PC12 cells.
The activity of NFATc family transcription factors is tightly regulated in T cells via signaling pathways initiated by stimulation of the T cell receptor or its downstream effectors such as the Pim-1 serine/threonine kinase. Here, we demonstrate that NFATc-dependent transcription is inducible also in NGF-differentiated rat PC12 pheochromocytoma cells treated with phorbol esthers, calcium ionophores and/or forskolin and that the Pim-1 kinase can further potentiate the effects of these agents. PC12 cells share many characteristics with sympathetic neurons and can be induced to produce and release catecholamines, such as dopamine and noradrenaline, and inflammatory cytokines, such as interleukin 6. Interestingly, Pim-1 can synergize with forskolin-induced signaling pathways to stimulate also neuroendocrine functions of PC12 cells.
Glazova
Margarita
M
Turku Centre for Biotechnology, University of Turku/Abo Akademi University, Tykistökatu 6 B, FI-20520 Turku, Finland.
Aho
Teija L T
TL
Palmetshofer
Alois
A
Murashov
Alexander
A
Scheinin
Mika
M
Koskinen
Päivi J
PJ
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004357:Drug Synergism; D007476:Ionophores / Q000494:pharmacology; D050778:NFATC Transcription Factors; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010703:Phorbol Esters / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051573:Proto-Oncogene Proteins c-pim-1; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*
D002395:Catecholamines; D016207:Cytokines; D004268:DNA-Binding Proteins; D007476:Ionophores; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010703:Phorbol Esters; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D005576:Colforsin; D020932:Nerve Growth Factor; C496637:Pim1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1