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 ch annels, or stimulating release of second messengers. Recently, calcitr iol (the hormonal form of vitamin D) has been shown to stimulate the e nzymatic activity of a nonreceptor protein tyrosine kinase, Src, in ke ratinocytes and colonocytes. This mode of signal transduction resemble s that utilized by membrane receptors devoid of intrinsic tyrosine kin ase activity. There is evidence that calcitriol-activated Src plays an important role in signal transduction due to the activation of protei n kinase C isozymes or a mitogen-activated protein kinase cascade. Src -mediated signaling, therefore, may be an important mediator of the ph ysiological and pharmacological effects of calcitriol. The synthesis o f vitamin D analogs capable of selective activation or inhibition of t he Src-mediated signaling pathway(s) may be a new, promising approach to expanding the therapeutic scope and clinical utility of these compo unds. BIOCHEM PHARMACOL 56;10:1273-1277, 1998. (C) 1998 Elsevier Scien ce Inc.