Selected glimpses into the activation and function of Src kinase

Since the discovery of the v-src and c-src genes and their products, much p rogress has been made in the elucidation of the structure, regulation, loca lization, and function of the Src protein. Src is a non-receptor protein ty rosine kinase that transduces signals that are involved in the control of a variety of cellular processes such as proliferation, differentiation, moti lity, and adhesion. Src is normally maintained in an inactive state, but ca n be activated transiently during cellular events such as mitosis, or const itutively by abnormal events such as mutation (i.e, v-Src and some human ca ncers). Activation of Src occurs as a result of disruption of the negative regulatory processes that normally suppress Src activity, and understanding the various mechanisms behind Src activation has been a target of intense study. Src associates with cellular membranes, in particular the plasma mem brane, and endosomal membranes. Studies indicate that the different subcell ular localizations of Src could be important for the regulation of specific cellular processes such as mitogenesis, cytoskeletal organization, and/or membrane trafficking. This review will discuss the history behind the disco very and initial characterization of Src and the regulatory mechanisms of S rc activation, in particular, regulation by modification of the carboxyterm inal regulatory tyrosine by phosphatases and kinases, Its focus will then t urn to the different subcellular localizations of Src and the possible role s of nuclear and perinuclear targets of Src, Finally, a brief section will review some of our present knowledge regarding Src involvement in human can cers.