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Review
. 2015 Mar:147:81-4.
doi: 10.1016/j.jsbmb.2014.11.002. Epub 2014 Nov 6.

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

Maryam Doroudi  1 , Zvi Schwartz  2 , Barbara D Boyan  3
Affiliations
Review

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

Maryam Doroudi et al. J Steroid Biochem Mol Biol. 2015 Mar.

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.

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Figures

Figure 1
Figure 1
Effects of Pdia3, Vdr and Cav-1 silencing on 1α,25(OH)2D3-stimulated PKC activation in MC3T3-E1 osteoblasts. The data show treatment vs. vehicle ratios. *p<0.05, vs. vehicle; $p<0.05, vs. 1α,25(OH)2D3 treated WT.
Figure 2
Figure 2
Effects of Plaa silencing on CaMKII, PLA2 and PKC activation, and PGE2 release in MC3T3-E1 osteoblast in response to 1α,25(OH)2D3. The data show treatment vs. vehicle ratios. The dashed line represents the vehicle control (dashed line=1). *p<0.05, treatment vs. control; #p<0.05, WT vs. ShPlaa.
Figure 3
Figure 3
Effects of Camk2a silencing on CaMKII, PLA2 and PKC activation, and PGE2 release in MC3T3-E1 osteoblast cells. The data show treatment vs. vehicle ratios. The dashed line represents the vehicle control (dashed line=1). *p<0.05, treatment vs. control; #p<0.05, WT vs. ShCamk2a.
Figure 4
Figure 4
Overview of 1α,25(OH)2D3 membrane-mediated pathway.
See this image and copyright information in PMC

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