Biomaterial Database

Redistribution of activated pp60c-src to integrin-dependent cytoskeletal complexes in thrombin-stimulated platelets. 1993

E A Clark, and J S Brugge

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104.

Thrombin stimulation of platelets induces a transient increase in the specific activity of pp60c-src followed by a redistribution of pp60c-src to the Triton X-100-insoluble, cytoskeleton-rich fraction. Concomitant with the observed increase in pp60c-src activity was a rapid dephosphorylation of tyrosine 527 in 10 to 15% of pp60c-src molecules. In addition, we found that pp60c-src from the Triton-insoluble fraction was phosphorylated on tyrosine 416, the autophosphorylation site which is phosphorylated in activated oncogenic variants of pp60src. Furthermore, in platelets from patients with Glanzmann's thrombasthenia (which are deficient in the integrin receptor GPIIb-IIIa), pp60c-src was not translocated to the Triton-insoluble fraction, and there was a sustained increase in pp60c-src activity following thrombin treatment. These results suggest that pp60c-src is rapidly activated in thrombin-stimulated platelets, potentially by a protein tyrosine phosphatase, before it translocates to a cytoskeletal fraction, where many of its potential substrates are found. The evidence that the cytoskeletal association of pp60c-src is dependent upon engagement of the integrin receptor GPIIb-IIIa suggests that integrin-cytoskeletal complexes may serve to compartmentalize and anchor activated enzymes involved in signal transduction.

UI	MeSH Term	Description	Entries
D010980	Platelet Membrane Glycoproteins	Surface glycoproteins on platelets which have a key role in hemostasis and thrombosis such as platelet adhesion and aggregation. Many of these are receptors.	PM-GP,Platelet Glycoprotein,Platelet Membrane Glycoprotein,PM-GPs,Platelet Glycoproteins,Glycoprotein, Platelet,Glycoprotein, Platelet Membrane,Glycoproteins, Platelet,Glycoproteins, Platelet Membrane,Membrane Glycoprotein, Platelet,Membrane Glycoproteins, Platelet,PM GP
D011092	Polyethylene Glycols	Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.	Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D011505	Protein-Tyrosine Kinases	Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.	Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D002451	Cell Compartmentation	A partitioning within cells due to the selectively permeable membranes which enclose each of the separate parts, e.g., mitochondria, lysosomes, etc.	Cell Compartmentations,Compartmentation, Cell,Compartmentations, Cell
D003599	Cytoskeleton	The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.	Cytoplasmic Filaments,Cytoskeletal Filaments,Microtrabecular Lattice,Cytoplasmic Filament,Cytoskeletal Filament,Cytoskeletons,Filament, Cytoplasmic,Filament, Cytoskeletal,Filaments, Cytoplasmic,Filaments, Cytoskeletal,Lattice, Microtrabecular,Lattices, Microtrabecular,Microtrabecular Lattices
D005340	Fibrinogen	Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.	Coagulation Factor I,Factor I,Blood Coagulation Factor I,gamma-Fibrinogen,Factor I, Coagulation,gamma Fibrinogen
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001692	Biological Transport	The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.	Transport, Biological,Biologic Transport,Transport, Biologic
D012995	Solubility	The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Solubilities
D013915	Thrombasthenia	A congenital bleeding disorder with prolonged bleeding time, absence of aggregation of platelets in response to most agents, especially ADP, and impaired or absent clot retraction. Platelet membranes are deficient in or have a defect in the glycoprotein IIb-IIIa complex (PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX).	Glanzmann Thrombasthenia,Deficiency of GP 2b 3a Complex,GP IIb-IIIa Complex, Deficiency Of,Glanzmann Thrombasthenia, Type A,Glycoprotein Complex IIb-IIIa, Deficiency Of,Platelet Fibrinogen Receptor, Deficiency of,Platelet Glycoprotein 2b-3a Deficiency,Platelet Glycoprotein IIb-IIIa Deficiency,Thrombasthenia of Glanzmann and Naegeli,GP IIb IIIa Complex, Deficiency Of,Glycoprotein Complex IIb IIIa, Deficiency Of,Platelet Glycoprotein 2b 3a Deficiency,Platelet Glycoprotein IIb IIIa Deficiency,Thrombasthenia, Glanzmann,Thrombasthenias

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