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PMID: 1545823 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nuclear localization and regulation of erk- and rsk-encoded protein kinases.

Molecular and cellular biology ·Vol. 12 ·No. 3 ·1992-03-00 ·Pages 915-27

Chen RH, Sarnecki C, Blenis J

Abstract

We demonstrate that members of the erk-encoded family of mitogen-activated protein (MAP) kinases (pp44/42mapk/erk) and members of the rsk-encoded protein kinases (RSKs or pp90rsk) are present in the cytoplasm and nucleus of HeLa cells. Addition of growth factors to serum-deprived cells results in increased tyrosine and threonine phosphorylation and in the activation of cytosolic and nuclear MAP kinases. Activated MAP kinases then phosphorylate (serine/threonine) and activate RSKs. Concurrently, a fraction of the activated MAP kinases and RSKs enter the nucleus. In addition, a distinct growth-regulated RSK-kinase activity (an enzyme[s] that phosphorylates recombinant RSK in vitro and that may be another member of the erk-encoded family of MAP kinases) was found associated with a postnuclear membrane fraction. Regulation of nuclear MAP kinase and RSK activities by growth factors and phorbol ester is coordinate with immediate-early gene expression. Indeed, in vitro, MAP kinase and/or RSK phosphorylates histone H3 and the recombinant c-Fos and c-Jun polypeptides, transcription factors phosphorylated in a variety of cells in response to growth stimuli. These in vitro studies raise the possibility that the MAP kinase/RSK signal transduction pathway represents a protein-Tyr/Ser/Thr phosphorylation cascade with the spatial distribution and temporal regulation that can account for the rapid transmission of growth-regulating information from the membrane, through the cytoplasm, and to the nucleus.

MeSH Terms
Amino Acid Sequence Calcium-Calmodulin-Dependent Protein Kinases Cell Division Cell Fractionation Cell Nucleus/enzymology Cytosol/enzymology Fluorescent Antibody Technique Gene Expression Regulation, Enzymologic HeLa Cells Humans Immunoblotting Molecular Sequence Data Protein Kinases/genetics,metabolism Protein-Tyrosine Kinases/genetics,metabolism Proteins/genetics,metabolism Ribosomal Protein S6 Kinases, 90-kDa Signal Transduction Substrate Specificity
Chemicals
Proteins Protein Kinases Protein-Tyrosine Kinases RPS6KA1 protein, human Ribosomal Protein S6 Kinases, 90-kDa ribosomal protein S6 kinase, 90kDa, polypeptide 3 Calcium-Calmodulin-Dependent Protein Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chen R H
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts 02115.
Sarnecki C
Blenis J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.12.3.915-927.1992
Published
1992-03-00
Pages
915-27
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC369523
Subset
IM
Grants
NCI NIH HHS · CA-46595 · United States
External Links
PubMed source DOI: 10.1128/mcb.12.3.915-927.1992 PMC Full Text View journal details
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