Kramer I M, Koornneef I, de Laat S W, van den Eijnden-van Raaij A J
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, The Netherlands.
EMBO J. 1991 May;10(5):1083-9. doi: 10.1002/j.1460-2075.1991.tb08048.x.
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.
β型转化生长因子是一类调节生长和分化的多肽家族。转化生长因子-β(TGF-β)通过与特定细胞表面受体相互作用对靶细胞发挥作用,但其信号转导途径目前很大程度上仍未明确。在本研究中,我们报告TGF-β1可诱导水貂肺CCl64细胞中环磷酸腺苷反应元件结合蛋白(CREB)的快速磷酸化。TGF-β1诱导的磷酸化不是由环磷酸腺苷依赖性蛋白激酶介导的。与CREB磷酸化增加平行,观察到与胶原酶佛波酯反应元件(TPA responsive element, TRE)的结合增加。CREB可能作为与另一种未知蛋白质的异二聚体参与与该元件的结合。对CREB的修饰及其参与增强的TRE结合可能是TGF-β1诱导TRE介导的转录激活的一种机制。