Proteomic Approaches to the Analysis of Early Events in Colony-stimulating Factor-1 Signal Transduction

Abstract

The exposure of cells to growth factors leads to the rapid tyrosine phosphorylation of proteins that play critical roles in initiating cellular responses. These proteins are associated with other nontyrosine-phosphorylated pro-teins. Together, they represent less than 0.02 % of the total cellular protein. To study their functions in growth factor signaling it is necessary to establish their identity, post-translational modifications, and interactions. We have focused on the characterization of this group of proteins during the early response of macrophages to the macrophage growth factor, colony-stimulating factor-1 (CSF-1). We review here the development of approaches to analysis of the rapid CSF-1-induced changes in the CSF-1 receptor tyrosine kinase and phosphotyrosyl sig-naling complexes. Recent advances in mass spectrome-try technology are greatly facilitating the characterization of such complexes. These methods strongly support and enhance genetic approaches that are being used to ana-lyze the function of individual signaling components an