title: The Src family kinases, Fgr, Fyn, Lck, and Lyn, colocalize with coated membranes in platelets.
abstract: Nonreceptor protein tyrosine kinases phosphorylate proteins, thereby activating many intracellular signaling pathways and mediating protein-protein interactions. Protein phosphorylation is regulated in large part by the subcellular localization of these kinases and their respective substrates. Src is the most studied of these kinases, although other members of the Src family have been shown to be important in the differentiation of specific cell types. Src and Src family members are reported to be membrane-associated, but detergent-extraction studies have demonstrated a major difference in the solubility of Src compared with other members of the Src family (Fgr, Fyn, Lck, Lyn, and Yes), suggesting that their subcellular distributions may be different. By immunoelectron microscopy, we demonstrate that, unlike Src, the Src-related kinases are associated with electron-dense cytoplasmic domains and plasma membrane domains that correspond in size and frequency to endocytotic 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 association with this class of endocytotic vesicle. We hypothesize that this vesicular association of Src-related kinases indicates a role for them in the endocytotic vesicle-mediated uptake and trafficking of plasma proteins into platelet granules.
authors.affiliation: Department of Pathology, Oregon Health Sciences University, Portland 97201, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Stenberg
authors.forename: T I
authors.initials: TI
authors.lastname: Pestina
authors.forename: R J
authors.initials: RJ
authors.lastname: Barrie
authors.forename: C W
authors.initials: CW
authors.lastname: Jackson
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D003034:Coated Pits, Cell-Membrane / Q000201:enzymology*; D004705:Endocytosis; D005260:Female; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000201:enzymology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D016253:Microscopy, Immunoelectron; D011518:Proto-Oncogene Proteins / Q000097:blood; D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D019061:src-Family Kinases / Q000097:blood*
chemical_list: D011518:Proto-Oncogene Proteins; C494961:Fyn protein, rat; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D051575:Proto-Oncogene Proteins c-yes; D016392:Proto-Oncogene Proteins pp60(c-src); C060902:lyn protein-tyrosine kinase; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases