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A unique phosphorylation-dependent mechanism for the activation of Ca2+/calmodulin-dependent protein kinase type IV/GR.

Publication ,  Journal Article
Chatila, T; Anderson, KA; Ho, N; Means, AR
Published in: J Biol Chem
August 30, 1996

The activity of the Ca2+/calmodulin-dependent protein kinase IV/Gr (CaMKIV/Gr) is shown to be strictly regulated by phosphorylation of three residues both in vitro and in response to antigen receptor-mediated signaling in lymphocytes. One residue, Thr-200, is indispensable for enhancement of Ca2+/calmodulin-dependent basal activity by CaMKIV/Gr kinase. This event requires Ca2+/calmodulin in the full-length CaMKIV/Gr but is Ca2+/calmodulin-independent when a truncated version of CaMKIV/Gr is used as a substrate (DeltaCaMKIV/Gr1-317 (Delta1-317)). The other two residues, Ser12 and Ser13, are apparently autophosphorylated by the Ca2+/calmodulin-bound CaMKIV/Gr. Phosphorylation of neither Ser12-Ser13 nor Thr312 (the residue in a homologous position to Thr286 of CaMKIIalpha influences the development of Ca2+/calmodulin-independent activity or any other property of CaMKIV/Gr examined. Similarly, removal of the NH2-terminal 20 amino acids has no effect on the activation or function of CaMKIV/Gr. However, mutation of both Ser12 and Ser13 residues to Ala in Delta1-317 completely abrogates activity, while individual substitutions have no effect. These results indicate that the NH2-terminal Ser cluster mediates a novel type of intrasteric inhibition and suggest that three events are required for CaMKIV/Gr activation: 1) Ca2+/calmodulin binding; 2) phosphorylation of the Ca2+/calmodulin-bound enzyme on Thr200 by a Ca2+/calmodulin-dependent protein kinase kinase; and 3) autophosphorylation of Ser12-Ser13. This three-step requirement is unique among the multifunctional Ca2+/calmodulin-dependent kinases.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

August 30, 1996

Volume

271

Issue

35

Start / End Page

21542 / 21548

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Recombinant Proteins
  • Phosphorylation
  • Mutagenesis, Site-Directed
  • Humans
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4
  • Biochemistry & Molecular Biology
  • 34 Chemical sciences
  • 32 Biomedical and clinical sciences
 

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Chatila, T., Anderson, K. A., Ho, N., & Means, A. R. (1996). A unique phosphorylation-dependent mechanism for the activation of Ca2+/calmodulin-dependent protein kinase type IV/GR. J Biol Chem, 271(35), 21542–21548. https://doi.org/10.1074/jbc.271.35.21542
Chatila, T., K. A. Anderson, N. Ho, and A. R. Means. “A unique phosphorylation-dependent mechanism for the activation of Ca2+/calmodulin-dependent protein kinase type IV/GR.J Biol Chem 271, no. 35 (August 30, 1996): 21542–48. https://doi.org/10.1074/jbc.271.35.21542.
Chatila T, Anderson KA, Ho N, Means AR. A unique phosphorylation-dependent mechanism for the activation of Ca2+/calmodulin-dependent protein kinase type IV/GR. J Biol Chem. 1996 Aug 30;271(35):21542–8.
Chatila, T., et al. “A unique phosphorylation-dependent mechanism for the activation of Ca2+/calmodulin-dependent protein kinase type IV/GR.J Biol Chem, vol. 271, no. 35, Aug. 1996, pp. 21542–48. Pubmed, doi:10.1074/jbc.271.35.21542.
Chatila T, Anderson KA, Ho N, Means AR. A unique phosphorylation-dependent mechanism for the activation of Ca2+/calmodulin-dependent protein kinase type IV/GR. J Biol Chem. 1996 Aug 30;271(35):21542–21548.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

August 30, 1996

Volume

271

Issue

35

Start / End Page

21542 / 21548

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Recombinant Proteins
  • Phosphorylation
  • Mutagenesis, Site-Directed
  • Humans
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Type 4
  • Biochemistry & Molecular Biology
  • 34 Chemical sciences
  • 32 Biomedical and clinical sciences