title: Identification of the Src family kinases, Lck and Fgr in platelets. Their tyrosine phosphorylation status and subcellular distribution compared with other Src family members.
abstract: We have identified the Src family members, Lck and Fgr in resting human and rodent platelets and compared their subcellular distributions and tyrosine phosphorylation status to those of the other Src family kinases to gain insights into the signal transduction pathways active in maintaining platelets in the circulation. Like Fyn, Lyn, and Yes, most of Fgr and Lck was detergent-insoluble in human and rat platelets. In comparison, Src showed higher detergent solubility than the Src-related kinases. Most all human platelet Src was detergent-soluble, while that of rodent platelets was present in all detergent fractions. We also compared the tyrosine-phosphorylation status of Lck and Fgr to other Src family members in resting platelets using immunoprecipitation and immunoblotting. All of these Src family members except Fgr exhibited substantial phosphotyrosine antibody labeling. The partitioning of these kinases, with the exception of Src, with the detergent-insoluble fraction, their tyrosine-phosphorylation status, and co-localization with endocytotic vesicles lead us to hypothesize that the Src family kinases are involved in signaling events that drive cytoskeletal reorganization and active endocytosis of plasma proteins by circulating platelets.
authors.affiliation: Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, TN, USA. tamara.pestina@stjude.org
authors.forename: T I
authors.initials: TI
authors.lastname: Pestina
authors.forename: P E
authors.initials: PE
authors.lastname: Stenberg
authors.forename: B J
authors.initials: BJ
authors.lastname: Druker
authors.forename: S A
authors.initials: SA
authors.lastname: Steward
authors.forename: N K
authors.initials: NK
authors.lastname: Hutson
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*; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004705:Endocytosis; D004790:Enzyme Induction; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000097:blood; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D012995:Solubility; D013045:Species Specificity; D013347:Subcellular Fractions / Q000201:enzymology; D019061:src-Family Kinases / Q000097:blood
chemical_list: D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D019000:Phosphotyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases