The signal-dependent coactivator CBP is a nuclear target for pp90RSK.
We have examined the mechanism by which growth factor-mediated induction of the Ras pathway interferes with signaling via the second messenger cAMP. Activation of cellular Ras with insulin or NGF stimulated recruitment of the S6 kinase pp90RSK to the signal-dependent coactivator CBP. Formation of the pp90RSK-CBP complex occurred with high stoichiometry and persisted for 6-8 hr following growth factor addition. pp90RSK specifically recognized the E1A-binding domain of the coactivator CBP. In addition, like E1A, binding of pp90RSK to CBP was sufficient to repress transcription of cAMP-responsive genes via the cAMP-inducible factor CREB. By contrast with its effects on the cAMP pathway, formation of the pp90RSK-CBP complex was required for induction of Ras-responsive genes. These results provide a demonstration of cross-coupling between two signaling pathways that occurs at the level of a signal-dependent coactivator.
Nakajima
T
T
Department of Cellular and Molecular Physiology Harvard Medical School Boston, Massachusetts 02115, USA.
Fukamizu
A
A
Takahashi
J
J
Gage
F H
FH
Fisher
T
T
Blenis
J
J
Montminy
M R
MR
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D050882:CREB-Binding Protein; D002454:Cell Differentiation; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005786:Gene Expression Regulation; D007328:Insulin / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D016716:PC12 Cells; D010957:Plasmids; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
D017500:Adenovirus E1A Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D007328:Insulin; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D005576:Colforsin; D000242:Cyclic AMP; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D018631:ras Proteins