THE SRC FAMILY KINASES, FGR, FYN, LCK, AND LYN, COLOCALIZE WITH COATED MEMBRANES IN PLATELETS

Nonreceptor protein tyrosine kinases phosphorylate proteins, thereby a ctivating many intracellular signaling pathways and mediating protein- protein interactions, Protein phosphorylation is regulated in large pa rt by the subcellular localization of these kinases and their respecti ve substrates. Src is the most studied of these kinases, although othe r members of the Src family have been shown to be important in the dif ferentiation of specific cell types, Src and Src family members are re ported to be membrane-associated, but detergent-extraction studies hav e demonstrated a major difference in the solubility of Src compared wi th other members of the Src family (Fgr, Fyn, Lck, Lyn, and Yes), sugg esting that their subcellular distributions may be different. By immun oelectron microscopy, we demonstrate that, unlike Src, the Src-related kinases are associated with electron-dense cytoplasmic domains and pl asma membrane domains that correspond in size and frequency to endocyt otic vesicles and coated pits, Clusters of labeling for these kinases also were seen adjacent to granule membranes. These kinases colocalize with the coated vesicle protein, clathrin, confirming their associati on with this class of endocytotic vesicle. We hypothesize that this ve sicular association of Src-related kinases indicates a role for them i n the endocytotic vesicle-mediated uptake and trafficking of plasma pr oteins into platelet granules. (C) 1997 by The American Society of Hem atology.