Binding of galectin-1 to alfa2bbeta3 integrin triggers "outside-in" signals, stimulates platelet activation, and controls primary hemostasis.

ROMANIUK MA; CROCI DO; LAPPONI MJ; TRIBULATTI MV; NEGROTTO S; POIRIER F; CAMPETELLA O; RABINOVICH GA; SCHATTNER M.

FASEB JOURNAL

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2012 p. 2788 - 2798

0892-6638

Abstract Understanding noncanonical mechanisms of platelet activation represents an important challenge for the identification of novel therapeutic targets in bleeding disorders, thrombosis, and cancer. We previously reported that galectin-1 (Gal-1), a ¥â-galactoside-binding protein, triggers platelet activation in vitro. Here we investigated the molecular mechanisms underlying this function and the physiological relevance of endogenous Gal-1 in hemostasis. Mass spectrometry analysis, as well as studies using blocking antibodies against the anti-¥á(IIb) subunit of¥á(IIb)¥â(3) integrin or platelets from patients with Glanzmann¢¥s thrombasthenia syndrome (¥á(IIb)¥â(3) deficiency), identified this integrin as a functional Gal-1 receptor in platelets. Binding of Gal-1 to platelets triggered the phosphorylation of ¥â(3)-integrin, Syk, MAPKs, PI3K, PLC¥ã2, thromboxane (TXA(2)) release, and Ca(2+) mobilization. Not only soluble but also immobilized Gal-1 promoted platelet activation. Gal-1-deficient (Lgals1(-/-)) mice showed increased bleeding time (P