Characterization of an autoinhibitory domain in human mitogen-activated protein kinase-activated protein kinase 2. Academic Article uri icon

Overview

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.

publication date

  • January 6, 1995

Research

keywords

  • Peptides
  • Protein Serine-Threonine Kinases

Identity

Scopus Document Identifier

  • 0028883299

Digital Object Identifier (DOI)

  • 10.1074/jbc.270.1.202

PubMed ID

  • 7814374

Additional Document Info

volume

  • 270

issue

  • 1