Beta 3 integrin-mediated fibrin clot retraction by nucleated cells: differing behavior of alpha IIb beta 3 and alpha v beta 3.
Fibrin clot retraction may be important in resolution of thrombi and, in platelets, is mediated by integrin alpha IIb beta 3 (GPIIb-IIIa). Nucleated cells that lack alpha IIb beta 3 can retract fibrin clots, and we now report that integrin alpha v beta 3 can support this process. In addition, we compared the capacities of recombinant beta 3 integrins to mediate clot retraction in Chinese hamster ovary and M21 melanoma cells. We found that alpha v beta 3, but not alpha IIb beta 3, could spontaneously support retraction. Transferring the cytoplasmic domain of alpha v to alpha IIb enabled the resulting chimeric alpha IIb beta 3 to support clot retraction. The capacity of the alpha v cytoplasmic domain to support clot retraction was not caused by activation of the ligand binding function of alpha IIb beta 3 or by enhancement of alpha IIb beta 3's capacity to stimulate the formation of focal adhesions or the tyrosine phosphorylation of pp125FAK. These experiments define requirements for alpha IIb beta 3-mediating clot retraction, establish the capacity of alpha v beta 3 to mediate this process, and suggest differing functional roles of the alpha v and alpha IIb cytoplasmic domains.
Chen
Y P
YP
Department of Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
O'Toole
T E
TE
Leong
L
L
Liu
B Q
BQ
Diaz-Gonzalez
F
F
Ginsberg
M H
MH
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D016466:CHO Cells; D002460:Cell Line; D003018:Clot Retraction; D006224:Cricetinae; D004730:Endothelium, Vascular; D005337:Fibrin / Q000502:physiology*; D005340:Fibrinogen / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007163:Immunosorbent Techniques; D039661:Integrin beta3; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D008545:Melanoma; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D016024:Receptors, Cytoadhesin / Q000235:genetics / Q000502:physiology*; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D015703:Antigens, CD; D039661:Integrin beta3; D016023:Integrins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; D005337:Fibrin; D005340:Fibrinogen