Membrane-mediated actions of 1,25-dihydroxy vitamin D3: a review of the roles of phospholipase A2 activating protein and Ca(2+)/calmodulin-dependent protein kinase II

J Steroid Biochem Mol Biol. 2015 Mar:147:81-4. doi: 10.1016/j.jsbmb.2014.11.002. Epub 2014 Nov 6.

Abstract

The secosteroid 1α,25-dihydroxy vitamin D3 [1α,25(OH)2D3] acts on cells via classical steroid hormone receptor-mediated gene transcription and by initiating rapid membrane-mediated signaling pathways. In its membrane-initiated pathway, after 1α,25(OH)2D3 interacts with protein disulfide isomerase, family A, member 3 (Pdia3) in caveolae, phospholipase A2 (PLA2) and protein kinase C (PKC) are activated. Recent efforts to determine the signaling proteins involved in the 1α,25(OH)2D3 signal from Pdia3 to PLA2 have indicated that phospholipase A2 activating protein (PLAA) and Ca(2+)/calmodulin-dependent kinase II (CaMKII) are required. PLAA is located in caveolae, where it interacts with Pdia3 and caveolin-1 (Cav-1) to initiate rapid signaling via CaMKII, activating PLA2, leading to activation of protein kinase C (PKC) and PKC-dependent responses.

Keywords: 1α,25(OH)(2)D(3); Ca(2+)/calmodulin-dependent protein kinase II; PDIA3; PLA(2); PLAA; Protein kinase C.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcitriol / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cell Membrane / metabolism
  • Enzyme Activation
  • Gene Silencing
  • Humans
  • Phospholipases A2 / metabolism
  • Protein Kinase C / metabolism
  • Proteins / genetics
  • Proteins / metabolism*
  • Signal Transduction

Substances

  • Proteins
  • phospholipase A2-activating protein
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Phospholipases A2
  • Calcitriol