Modulation of the affinity of integrin alpha IIb beta 3 (GPIIb-IIIa) by the cytoplasmic domain of alpha IIb.
Intracellular signaling alters integrin adhesive functions in inflammation, immune responses, hemostasis, thrombosis, and retinal development. By truncating the cytoplasmic domain of alpha IIb, the affinity of integrin alpha IIb beta 3 for ligand was increased. Reconstitution with the cytoplasmic domain from integrin alpha 5 did not reverse the increased affinity. Thus, the cytoplasmic domain of the alpha subunit of GPIIb-IIIa controls ligand binding affinity, which suggests mechanisms for inside-out transmembrane signaling through integrins. These findings imply the existence of hitherto unappreciated hereditary and acquired thrombotic disorders in humans.
O'Toole
T E
TE
Committee on Vascular Biology, Scripps Research Institute, La Jolla, CA 92037.
Mandelman
D
D
Forsyth
J
J
Shattil
S J
SJ
Plow
E F
EF
Ginsberg
M H
MH
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002449:Cell Aggregation; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D046911:Macromolecular Substances; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen