Secreted Alpha Granule Proteins

Mosher, Deane F.; Pesciotta, Donna M.; Loftus, Joseph C.; Albrecht, Ralph M.

doi:10.1007/978-1-4684-4880-1_8

Cited by 18 publications

(14 citation statements)

References 81 publications

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“…The effects of purified thrombospondin and ,6-thromboglobulin on bFGF-stimulated [3H] thymidine incorporation were examined at concentrations higher than these proteins when found in platelet releasate (28). Fig.…”

Section: Methodsmentioning

confidence: 99%

Platelet factor 4 modulates the mitogenic activity of basic fibroblast growth factor.

Watson

Getzler²,

Mosher³

1994

J. Clin. Invest.

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Section: Methodsmentioning

confidence: 99%

Platelet factor 4 modulates the mitogenic activity of basic fibroblast growth factor.

Watson

Getzler²,

Mosher³

1994

J. Clin. Invest.

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“…In vivo endothelial cell damage or denudation results in platelet adhesion with subsequent degranulation and the recruitment of additional platelets to form a plug. Platelet alpha granules contain numerous adhesive proteins, including von Willebrand factor, fibronectin, fibrinogen, and thrombospondin (TSP),' that are secreted upon platelet stimulation, bind to the platelet membrane, and mediate aggregation (20)(21)(22)(23)(24)(25)(26). Fibrinogen links aggregating platelets by binding to the glycoprotein IIb/IIIa complex (GPIIb/IIIa) on opposing membranes (27).…”

Section: Introductionmentioning

confidence: 99%

Isolation of the thrombospondin membrane receptor.

et al. 1987

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Thrombospondin (TSP), a 450-kD multifunctional glycoprotein with a broad tissue distribution, is secreted upon platelet stimulation, binds to the activated platelet surface, and supports platelet aggregation. We have identified and isolated an 88-kD membrane glycoprotein present in platelets, endothelial cells, monocytes, and a variety of human tumor cell lines that is the membrane binding site for TSP. Endogenous platelet TSP binding to thrombin-and ionophore-stimulated human platelets was inhibited in the presence of the monoclonal antibody OKM5. TSP binding to C32 melanoma cells and HT1080 fibrosarcoma cells was specific and also inhibitable with OKM5 Mab. Cell labeling followed by specific immnunoprecipitation demonstrated biosynthesis of a single 88-kD glycoprotein. Binding of TSP to the isolated membrane protein was specific and saturable. These studies identify an 88-kD membrane glycoprotein that reacts with the monoclonal antibody, OKM5, and may function as the cellular TSP receptor.

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“…69 An ingenious alternative theory to explain the development of fibrinogen binding sites after platelet activation is that GP llb-llla are simply hidden by other surface molecules in unstimulated platelets. 71 When platelets spread, their surface area increases enough to permit the fibrinogen to reach GP llb-llla. Possibly, shape change has a similar effect.…”

mentioning

confidence: 99%

Platelet activation.

Zucker¹,

Nachmias²

1985

Arteriosclerosis

205

101

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Platelets are discoidal cytoplasmic particles that respond to a variety of stimuli by developing filopodia and rounding up (shape change), developing the ability to bind fibrinogen from the medium, and, with strong stimuli such as thrombin and PAF-acether, secreting the contents of several types of granules. Arachidonic acid is cleaved from phospholipids by phospholipase A2 and converted by the platelets to endoperoxides, and then to thromboxane A2. The bound dimeric fibrinogen molecules probably cause aggregation by forming bridges between platelets. Aggregation is reinforced by secreted fibrinogen and thrombospondin, which binds the platelets, and by thromboxane A2 and endoperoxides, as well as secreted ADP, which cause additional receptor-mediated activation. The responses to these stimuli are initiated when the agonists bind to specific receptors on the plasma membrane. Subsequent steps resemble those in other types of responsive cells: breakdown of phosphatidylinositol bisphosphate into diacylglycerol, a stimulator of protein kinase C, and inositol-1,4,5-trisphosphate, recently shown to be a potent calcium ionophore. The response of shape change results from increased cytoplasmic Ca2+ which permits phosphorylation of one of the light chains of myosin by a calcium-calmodulin-dependent kinase, with resulting enhanced actin-myosin interaction. Secretion is associated with phosphorylation of a 40,000 to 47,000 dalton protein by the diacylglycerol-activated protein kinase C. These recent findings have increased our understanding of the mechanisms of platelet activation, but much remains to be learned. How do agonist-receptor complexes influence PIP2 breakdown? Is this indeed the first step in activation? What mediates adhesion of platelets to the injured blood vessel wall? Does transduction of this stimulus occur by the same mechanism as transduction of commonly used soluble stimuli? What is the role of the phosphorylated 40-47 K protein in secretion? What change in GP IIb-IIIa promotes their ability to bind fibrinogen? What is the role of calcium-activated protease? Of the phosphorylation of actin-binding protein? Progress is being made rapidly, and these questions may be answered within a few years.

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Secreted Alpha Granule Proteins

Cited by 18 publications

References 81 publications

Platelet factor 4 modulates the mitogenic activity of basic fibroblast growth factor.

Platelet factor 4 modulates the mitogenic activity of basic fibroblast growth factor.

Isolation of the thrombospondin membrane receptor.

Platelet activation.

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