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Myristoylation of calcineurin B is not required for function or interaction with immunophilin-immunosuppressant complexes in the yeast Saccharomyces cerevisiae.

Publication ,  Journal Article
Zhu, D; Cardenas, ME; Heitman, J
Published in: J Biol Chem
October 20, 1995

Calcineurin is a heterodimeric Ca2+/calmodulin-dependent protein phosphatase that regulates signal transduction and is the target of immunophilin-immunosuppressive drug complexes in T-lymphocytes and in yeast. Calcineurin is composed of a catalytic A subunit and a regulatory B subunit that is myristoylated at its amino terminus. We employed genetic and biochemical approaches to investigate the functional roles of myristoylation of calcineurin B (CNB1) in Saccharomyces cerevisiae. A calcineurin B mutant in which glycine 2 was substituted by alanine (CNB1-G2A) did not incorporate [3H]myristate when expressed in yeast. Both wild-type calcineurin B and the CNB1-G2A mutant protein are partially associated with membranes and cytoskeletal structures; hence, myristoylation is not required for these associations. In several independent genetic assays of calcineurin functions (recovery from alpha-factor arrest, survival during cation stress, and viability of a calcineurin-dependent strain), the nonmyristoylated CNB1-G2A mutant protein exhibited full biological activity. In vitro, both wild-type and CNB1-G2A mutant proteins formed complexes with both cyclophilin A-cyclosporin A (CsA) and FKBP12-FK506 that contained calcineurin A. Interestingly, expression of the nonmyristoylated CNB1-G2A mutant protein rendered yeast cells partially resistant to the immunosuppressant CsA, but not to FK506. This study demonstrates that calcineurin B myristoylation is not required for function, but may participate in inhibition by the cyclophilin A-CsA complex.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 20, 1995

Volume

270

Issue

42

Start / End Page

24831 / 24838

Location

United States

Related Subject Headings

  • Tacrolimus Binding Proteins
  • Tacrolimus
  • Structure-Activity Relationship
  • Saccharomyces cerevisiae
  • Peptidylprolyl Isomerase
  • Myristic Acids
  • Myristic Acid
  • Molecular Sequence Data
  • Immunosuppressive Agents
  • Heat-Shock Proteins
 

Citation

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Zhu, D., Cardenas, M. E., & Heitman, J. (1995). Myristoylation of calcineurin B is not required for function or interaction with immunophilin-immunosuppressant complexes in the yeast Saccharomyces cerevisiae. J Biol Chem, 270(42), 24831–24838. https://doi.org/10.1074/jbc.270.42.24831
Zhu, D., M. E. Cardenas, and J. Heitman. “Myristoylation of calcineurin B is not required for function or interaction with immunophilin-immunosuppressant complexes in the yeast Saccharomyces cerevisiae.J Biol Chem 270, no. 42 (October 20, 1995): 24831–38. https://doi.org/10.1074/jbc.270.42.24831.
Zhu, D., et al. “Myristoylation of calcineurin B is not required for function or interaction with immunophilin-immunosuppressant complexes in the yeast Saccharomyces cerevisiae.J Biol Chem, vol. 270, no. 42, Oct. 1995, pp. 24831–38. Pubmed, doi:10.1074/jbc.270.42.24831.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 20, 1995

Volume

270

Issue

42

Start / End Page

24831 / 24838

Location

United States

Related Subject Headings

  • Tacrolimus Binding Proteins
  • Tacrolimus
  • Structure-Activity Relationship
  • Saccharomyces cerevisiae
  • Peptidylprolyl Isomerase
  • Myristic Acids
  • Myristic Acid
  • Molecular Sequence Data
  • Immunosuppressive Agents
  • Heat-Shock Proteins