Publication Date:
1996-08-16
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xing, J -- Ginty, D D -- Greenberg, M E -- CA43855/CA/NCI NIH HHS/ -- NS34814-01/NS/NINDS NIH HHS/ -- P30-HD18655/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 1996 Aug 16;273(5277):959-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8688081" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
;
Cell Line
;
Cell Nucleus/metabolism
;
Cyclic AMP Response Element-Binding Protein/*metabolism
;
Epidermal Growth Factor/pharmacology
;
*Gene Expression Regulation
;
Growth Substances/*pharmacology
;
Humans
;
Molecular Sequence Data
;
Nerve Growth Factors/pharmacology
;
PC12 Cells
;
Phosphorylation
;
Protein-Serine-Threonine Kinases/*metabolism
;
Rats
;
Ribosomal Protein S6 Kinases
;
*Signal Transduction
;
Tetradecanoylphorbol Acetate/pharmacology
;
Transcriptional Activation
;
Transfection
;
Tumor Cells, Cultured
;
ras Proteins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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