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ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15.
Proc Natl Acad Sci U S A. 2007 Dec 11; 104(50):19837-42.PN

Abstract

The ERK pathway responds to extracellular stimuli and oncogenes by modulating cellular processes, including transcription, adhesion, survival, and proliferation. ERK has diverse substrates that carry out these functions. The processes that are modulated are determined in part by the substrates that ERK phosphorylates. We demonstrate that PEA-15 (phosphoprotein enriched in astrocytes, 15 kDa) targets ERK to RSK2 and thereby enhances RSK2 activation. PEA-15 independently bound ERK and RSK2 and increased ERK association with RSK2 in a concentration-dependent manner. PEA-15 increased RSK2 activity and CREB-mediated transcription, and this process was regulated by phosphorylation of PEA-15. Finally, phorbol ester stimulation of PEA-15-null lymphocytes resulted in impaired RSK2 activation that was rescued by exogenous PEA-15 expression. Therefore, PEA-15 functions as a scaffold to enhance ERK activation of RSK2, and this activity is regulated by phosphorylation. Thus, PEA-15 can integrate signal transduction to provide a specific physiological outcome from activation of the multipotent ERK MAP kinase pathway.

Authors+Show Affiliations

Department of Cell Biology and Neuroscience, Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 604 Allison Road, Piscataway, NJ 08854, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18077417

Citation

Vaidyanathan, Hema, et al. "ERK MAP Kinase Is Targeted to RSK2 By the Phosphoprotein PEA-15." Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 50, 2007, pp. 19837-42.
Vaidyanathan H, Opoku-Ansah J, Pastorino S, et al. ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15. Proc Natl Acad Sci USA. 2007;104(50):19837-42.
Vaidyanathan, H., Opoku-Ansah, J., Pastorino, S., Renganathan, H., Matter, M. L., & Ramos, J. W. (2007). ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15. Proceedings of the National Academy of Sciences of the United States of America, 104(50), 19837-42.
Vaidyanathan H, et al. ERK MAP Kinase Is Targeted to RSK2 By the Phosphoprotein PEA-15. Proc Natl Acad Sci USA. 2007 Dec 11;104(50):19837-42. PubMed PMID: 18077417.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15. AU - Vaidyanathan,Hema, AU - Opoku-Ansah,John, AU - Pastorino,Sandra, AU - Renganathan,Hema, AU - Matter,Michelle L, AU - Ramos,Joe W, Y1 - 2007/12/06/ PY - 2007/12/14/pubmed PY - 2008/1/12/medline PY - 2007/12/14/entrez SP - 19837 EP - 42 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 104 IS - 50 N2 - The ERK pathway responds to extracellular stimuli and oncogenes by modulating cellular processes, including transcription, adhesion, survival, and proliferation. ERK has diverse substrates that carry out these functions. The processes that are modulated are determined in part by the substrates that ERK phosphorylates. We demonstrate that PEA-15 (phosphoprotein enriched in astrocytes, 15 kDa) targets ERK to RSK2 and thereby enhances RSK2 activation. PEA-15 independently bound ERK and RSK2 and increased ERK association with RSK2 in a concentration-dependent manner. PEA-15 increased RSK2 activity and CREB-mediated transcription, and this process was regulated by phosphorylation of PEA-15. Finally, phorbol ester stimulation of PEA-15-null lymphocytes resulted in impaired RSK2 activation that was rescued by exogenous PEA-15 expression. Therefore, PEA-15 functions as a scaffold to enhance ERK activation of RSK2, and this activity is regulated by phosphorylation. Thus, PEA-15 can integrate signal transduction to provide a specific physiological outcome from activation of the multipotent ERK MAP kinase pathway. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/18077417/ERK_MAP_kinase_is_targeted_to_RSK2_by_the_phosphoprotein_PEA_15_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=18077417 DB - PRIME DP - Unbound Medicine ER -