TGF-beta 1 induces phosphorylation of the cyclic AMP responsive element binding protein in ML-CCl64 cells.
Type beta transforming growth factors represent a family of polypeptides that modulate growth and differentiation. TGF-beta exerts its effects on target cells through interaction with specific cell surface receptors, but the signal transduction pathways are largely unresolved as yet. In this study we report that TGF-beta 1 induces a rapid phosphorylation of the cyclic AMP responsive element binding protein (CREB) in mink lung CCl64 cells. Phosphorylation induced by TGF-beta 1 is not mediated by the cAMP-dependent protein kinase. Parallel to the increase in phosphorylation of CREB, an increase in binding to the collagenase TPA responsive element was observed. CREB participates in the binding to this element, probably as a heterodimer with another as yet unknown protein. The modification imposed on CREB and its involvement in an enhanced TRE-binding could be a mechanism by which TGF-beta 1 induces the TRE-mediated transcriptional activation.
Kramer
I M
IM
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, The Netherlands.
Koornneef
I
I
de Laat
S W
SW
van den Eijnden-van Raaij
A J
AJ
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D016384:Consensus Sequence; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D003012:Microbial Collagenase / Q000235:genetics; D008907:Mink; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D000071701:Regulatory Factor X Transcription Factors; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D005576:Colforsin; D003012:Microbial Collagenase