GSBS Student Publications

Title

Molecular determinants that mediate selective activation of p38 MAP kinase isoforms

GSBS Program

Biochemistry & Molecular Pharmacology

Publication Date

2000-03-16

UMMS Affiliation

Graduate School of Biomedical Sciences; Howard Hughes Medical Institute, Program in Molecular Medicine

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The p38 mitogen-activated protein kinase (MAPK) group is represented by four isoforms in mammals (p38alpha, p38beta2, p38gamma and p38delta). These p38 MAPK isoforms appear to mediate distinct functions in vivo due, in part, to differences in substrate phosphorylation by individual p38 MAPKs and also to selective activation by MAPK kinases (MAPKKs). Here we report the identification of two factors that contribute to the specificity of p38 MAPK activation. One mechanism of specificity is the selective formation of functional complexes between MAPKK and different p38 MAPKs. The formation of these complexes requires the presence of a MAPK docking site in the N-terminus of the MAPKK. The second mechanism that confers signaling specificity is the selective recognition of the activation loop (T-loop) of p38 MAPK isoforms. Together, these processes provide a mechanism that enables the selective activation of p38 MAPK in response to activated MAPKK.

DOI of Published Version

10.1093/emboj/19.6.1301

Source

EMBO J. 2000 Mar 15;19(6):1301-11. Link to article on publisher's site

Journal/Book/Conference Title

The EMBO journal

Related Resources

Link to article in PubMed

PubMed ID

10716930

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