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Science. 1996 Aug 16;273(5277):959-63.

Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase.

Author information

1
Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.

Abstract

A signaling pathway has been elucidated whereby growth factors activate the transcription factor cyclic adenosine monophosphate response element-binding protein (CREB), a critical regulator of immediate early gene transcription. Growth factor-stimulated CREB phosphorylation at serine-133 is mediated by the RAS-mitogen-activated protein kinase (MAPK) pathway. MAPK activates CREB kinase, which in turn phosphorylates and activates CREB. Purification, sequencing, and biochemical characterization of CREB kinase revealed that it is identical to a member of the pp90(RSK) family, RSK2. RSK2 was shown to mediate growth factor induction of CREB serine-133 phosphorylation both in vitro and in vivo. These findings identify a cellular function for RSK2 and define a mechanism whereby growth factor signals mediated by RAS and MAPK are transmitted to the nucleus to activate gene expression.

PMID:
8688081
[Indexed for MEDLINE]

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