Modulation of tyrosine phosphorylation signalling pathways by 1alpha,25(OH)2-vitamin D3.

Hormonally active vitamin D(3), 1alpha,25(OH)(2)D(3), interacts with the classic vitamin D nuclear receptor that regulates gene transcription and with a putative cell membrane receptor that mediates rapid biological responses. 1alpha,25(OH)(2)D(3) actions on target tissues regulate: mineral metabolism and intracellular Ca(2+); protein kinase cascades leading to cell proliferation, differentiation and apoptosis; muscle growth and contractility; and the immune system. There is evidence for underlying 1alpha,25(OH)(2)D(3)-mediated protein tyrosine phosphorylation signalling in bone, intestine, muscle, epidermal and cancer cells. Extracellular-signal-regulated kinases-1/2, p38 and/or c-jun N-terminal kinase pathways play important roles in mediating 1alpha,25(OH)(2)D(3) actions. Studies to elucidate key regulatory metabolic steps and crosstalk sites in these pathways would enhance our understanding of the significance of tyrosine phosphorylation cascades in normal 1alpha,25(OH)(2)D(3) physiology, pathophysiology and pharmacology.