Characterization of an autoinhibitory domain in human mitogen-activated protein kinase-activated protein kinase 2

Y. L. Zu, Y. Ai, C. K. Huang

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Mitogen-activated protein (MAP) kinase-activated protein kinase 2, a Ser/Thr kinase, is phosphorylated and activated by MAP kinase. Sequence analysis of a clone isolated from the human HL-60 cell line revealed a 370- amino acid protein with a proline-rich N terminus, a highly conserved catalytic domain, and a C-terminal region containing a MAP kinase phosphorylation site. To better understand how the kinase is regulated, mutation analysis was used to map the functional domain(s). The wild type recombinant kinase had a low basal activity as detected by phosphorylation of a substrate peptide derived from the N terminus of glycogen synthase. Deletion of the proline-rich N terminus showed little effect on the basal activity. Deletion of the C terminus resulted in a marked increase in catalytic activity either with or without the pretreatment of the kinase by MAP kinase. Further analysis indicated that amino acid residues 339-353 in the C-terminal region were acting as an autoinhibitory domain. A synthetic peptide (RVLKEDKERWEDVK-amide) derived from this autoinhibitory domain inhibited the kinase activity in a concentration-dependent manner. These results suggest a regulatory model for the kinase.

Original languageEnglish (US)
Pages (from-to)202-206
Number of pages5
JournalJournal of Biological Chemistry
Volume270
Issue number1
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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