Inhibition of cytosolic phospholipase A2 by annexin I: Specific interaction model and mapping of the interaction site

Seung Wook Kim, Hae Jin Rhee, Jesang Ko, Yeo Jeong Kim, Hyung Gu Kim, Jai Myung Yang, Eung Chil Choi, Doe Sun Na

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74 Citations (Scopus)


Annexins (ANXs) display regulatory functions in diverse cellular processes, including inflammation, immune suppression, and membrane fusion. However, the exact biological functions of ANXs still remain obscure. Inhibition of phospholipase A2 (PLA2) by ANX-I, a 346-amino acid protein, has been observed in studies with various forms of PLA2. "Substrate depletion" and "specific interaction" have been proposed for the mechanism of PLA2 inhibition by ANX-I. Previously, we proposed a specific interaction model for inhibition of a 100-kDa porcine spleen cytosolic form of PLA2 (cPLA2) by ANX-I (Kim, K. M., Kim, D. K., Park, Y. M., and Na, D. S. (1994) FEBS Lett. 343, 251-255). Herein, we present an analysis of the inhibition mechanism of cPLA2 by ANX-I in detail using ANX-I and its deletion mutants. Deletion mutants were produced in Escherichia coli, and inhibition of cPLA2 activity was determined. The deletion mutant ANX-I-(1-274), containing the N terminus to amino acid 274, exhibited no cPLA2 inhibitory activity, whereas the deletion mutant ANX-I-(275-346), containing amino acid 275 to the C terminus, retained full activity. The protein-protein interaction between cPLA 2 and ANX-I was examined using the deletion mutants by immunoprecipitation and mammalian two-hybrid methods. Full-length ANX-I and ANX-I-(275-346) interacted with the calcium-dependent lipid-binding domain of cPLA2. ANX-I-(1-274) did not interact with cPLA2. Immunoprecipitation of A549 cell lysate with anti-ANX-I antibody resulted in coprecipitation of cPLA2. These results are consistent with the specific interaction mechanism rather than the substrate depletion model. ANX-I may function as a negative regulator of cPLA2 in cellular signal transduction.

Original languageEnglish
Pages (from-to)15712-15719
Number of pages8
JournalJournal of Biological Chemistry
Issue number19
Publication statusPublished - 2001 May 11
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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