Nongenomic signaling by vitamin D: a new face of Src

It is well known that steroids are able to produce nongenomic effects on various cells, such as activating protein kinases, opening ionic channels, or stimulating release of second messengers. Recently, calcitriol (the hormonal form of vitamin D) has been shown to stimulate the enzymatic activity of a nonreceptor protein tyrosine kinase, Src, in keratinocytes and colonocytes. This mode of signal transduction resembles that utilized by membrane receptors devoid of intrinsic tyrosine kinase activity. There is evidence that calcitriol-activated Src plays an important role in signal transduction due to the activation of protein kinase C isozymes or a mitogen-activated protein kinase cascade. Src-mediated signaling, therefore, may be an important mediator of the physiological and pharmacological effects of calcitriol. The synthesis of vitamin D analogs capable of selective activation or inhibition of the Src-mediated signaling pathway(s) may be a new, promising approach to expanding the therapeutic scope and clinical utility of these compounds.