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

Hormonally active vitamin D-3, 1 alpha,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. 1 alpha,25(OH)(2)D-3 actions on target tissues regulate: mineral metabolism and intracellular Ca2+; protein kinase cascades leading to cell proliferation, differentiation and apoptosis; muscle growth and contractility; and the immune system. There is evidence for underlying 1 alpha,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 1 alpha,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 1 alpha,25(OH)(2)D-3 physiology, pathophysiology and pharmacology.