Contributions of the mitogen-activated protein (MAP) kinase backbone and phosphorylation loop to MEK specificity

Megan J. Robinson, Mangeng Cheng, Andrei Khokhlatchev, Doug Ebert, Natalie Ahn, Kun Liang Guan, Bernd Stein, Elizabeth Goldsmith, Melanie H. Cobb

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

To examine the specificity of MEKs for MAP kinase family members, we determined the abilities of several MEK isoforms to phosphorylate mutants of the MAP kinase ERK2 and the related kinase ERK3 which are modified in the phosphorylation loop. The ERK2 mutants included mutations of the two phosphorylation sites, mutations of the acidic residue between these two sites, and mutations that shorten the length of this loop. All mutants were tested for phosphorylation by six mammalian MEKs and compared with several wild type MAP kinases. MEK1 and MEK2 phosphorylate a majority of the ERK2 mutants. MEK2 but not MEK1 will phosphorylate ERK3. Alteration of the residue between the two phosphorylation sites neither dramatically affected the activity of MEK1 and MEK2 toward ERK2 nor conferred recognition by other MEKs. Likewise, reduction of the length of the phosphorylation loop only partially reduces recognition by MEK1 and MEK2 but does not promote recognition by other MEKs. Thus other yet to be identified factors must contribute to the specificity of MEK recognition of MAP kinases.

Original languageEnglish (US)
Pages (from-to)29734-29739
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number47
DOIs
StatePublished - 1996

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Phosphorylation
Mitogen-Activated Protein Kinase Kinases
Mitogen-Activated Protein Kinases
Mutation
Mitogen-Activated Protein Kinase 6
Aptitude
Protein Isoforms

ASJC Scopus subject areas

  • Biochemistry

Cite this

Contributions of the mitogen-activated protein (MAP) kinase backbone and phosphorylation loop to MEK specificity. / Robinson, Megan J.; Cheng, Mangeng; Khokhlatchev, Andrei; Ebert, Doug; Ahn, Natalie; Guan, Kun Liang; Stein, Bernd; Goldsmith, Elizabeth; Cobb, Melanie H.

In: Journal of Biological Chemistry, Vol. 271, No. 47, 1996, p. 29734-29739.

Research output: Contribution to journalArticle

Robinson, Megan J. ; Cheng, Mangeng ; Khokhlatchev, Andrei ; Ebert, Doug ; Ahn, Natalie ; Guan, Kun Liang ; Stein, Bernd ; Goldsmith, Elizabeth ; Cobb, Melanie H. / Contributions of the mitogen-activated protein (MAP) kinase backbone and phosphorylation loop to MEK specificity. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 47. pp. 29734-29739.
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AU - Khokhlatchev, Andrei

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AU - Ahn, Natalie

AU - Guan, Kun Liang

AU - Stein, Bernd

AU - Goldsmith, Elizabeth

AU - Cobb, Melanie H.

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