A review of 1α,25(OH)2D3 dependent Pdia3 receptor complex components in Wnt5a non-canonical pathway signaling

Maryam Doroudi, Rene Olivares-Navarrete, Barbara D. Boyan, Zvi Schwartz

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


Wnt5a and 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] regulate endochondral ossification. 1α,25(OH)2D3 initiates its calcium-dependent effects via its membrane-associated receptor, protein disulfide isomerase A3 (Pdia3). 1α,25(OH)2D3 binding to Pdia3 triggers the interaction between Pdia3 and phospholipase A2 (PLA2)-activating protein (PLAA), resulting in downstream activation of calcium/calmodulin-dependent protein kinase II (CaMKII), PLA2, and protein kinase C (PKC). Wnt5a initiates its calcium-dependent effects via binding its receptors Frizzled2 (FZD2) and Frizzled5 (FZD5) and receptor tyrosine kinase-like orphan receptor 2 (ROR2), activating intracellular calcium release and stimulating PKC and CaMKII. Recent efforts to determine the inter-relation between Wnt5a and 1α,25(OH)2D3 signaling pathways have demonstrated that Wnt5a signals through a CaMKII/PLA2/PGE2/PKC cascade in chondrocytes and osteoblasts in which the components of the Pdia3 receptor complex were required. Furthermore, ROR2, but not FZD2 or FZD5, was required to mediate the calcium-dependent actions of 1α,25(OH)2D3. This review provides evidence that 1α,25(OH)2D3 and Wnt5a mediate their calcium-dependent pathways via similar receptor components and proposes that these pathways may interact since they are competing for the same receptor complex components.

Original languageEnglish (US)
Pages (from-to)84-88
Number of pages5
JournalJournal of Steroid Biochemistry and Molecular Biology
StatePublished - Aug 1 2015


  • 1 25-Dihydroxyvitamin D3
  • Calmodulin
  • Phospholipase A2 activating protein
  • Protein disulfide isomerase A3
  • Protein kinase C
  • Wnt5a

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology


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