cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway.
Cyclic adenosine monophosphate (cAMP) has tissue-specific effects on growth, differentiation, and gene expression. We show here that cAMP can activate the transcription factor Elk-1 and induce neuronal differentiation of PC12 cells via its activation of the MAP kinase cascade. These cell type-specific actions of cAMP require the expression of the serine/threonine kinase B-Raf and activation of the small G protein Rap1. Rap1, activated by mutation or by the cAMP-dependent protein kinase PKA, is a selective activator of B-Raf and an inhibitor of Raf-1. Therefore, in B-Raf-expressing cells, the activation of Rap1 provides a mechanism for tissue-specific regulation of cell growth and differentiation via MAP kinase.
Vossler
M R
MR
Department of Medicine, Oregon Health Sciences University L-474, Portland 97201, USA.
Yao
H
H
York
R D
RD
Pan
M G
MG
Rim
C S
CS
Stork
P J
PJ
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002417:Cattle; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000201:enzymology; D000242:Cyclic AMP / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D015800:Protozoan Proteins / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C494114:Elk1 protein, rat; D011518:Proto-Oncogene Proteins; D015800:Protozoan Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; C065352:rhoptry associated protein, Plasmodium; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases