Echistatin inhibits pp72syk and pp125FAK phosphorylation in fibrinogen-adherent platelets.
The adhesion of ADP-stimulated platelets to immobilized fibrinogen induces the tyrosine phosphorylation of multiple proteins which include pp72syk and pp125FAK. The phosphorylation of these two proteins increases as function of time of platelet adhesion to fibrinogen; however, pp72syk results strongly phosphorylated already after 15 min, whereas pp125FAK reaches high levels of phosphorylation after 1 h of platelet adhesion. Phosphorylation of both proteins is only slightly detectable when platelets are held in suspension or when platelets are allowed to adhere to bovine serum albumin, a non-specific substrate. Echistatin, an Arg-Gly-Asp (RGD)-containing snake-venom protein, affects protein tyrosine phosphorylation promoted by platelet adhesion to fibrinogen, by causing an approximately 44% and 39% decrease of pp72syk and pp125FAK phosphorylation, respectively. The interaction of echistatin with fibrinogen receptor glycoprotein IIb-IIIa on platelet surface might be responsible for the block of integrin-mediated signaling cascade, including pp72syk and pp125FAK inactivation.
Staiano
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Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy.
Della Morte
R
R
Di Domenico
C
C
Tafuri
S
S
Squillacioti
C
C
Belisario
M A
MA
Di Natale
P
P
D001792:Blood Platelets / Q000201:enzymology; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000097:blood / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors* / Q000097:blood; D005340:Fibrinogen / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology*; D000072377:Syk Kinase
D015815:Cell Adhesion Molecules; D004792:Enzyme Precursors; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; C057986:echistatin; D005340:Fibrinogen; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C000606896:SYK protein, human; D000072377:Syk Kinase