Beta 3-endonexin, a novel polypeptide that interacts specifically with the cytoplasmic tail of the integrin beta 3 subunit.
The adhesive and signaling functions of integrins are regulated through their cytoplasmic domains. We identified a novel 111 residue polypeptide, designated beta 3-endonexin, that interacted with the cytoplasmic tail of the beta 3 integrin subunit in a yeast two-hybrid system. This interaction is structurally specific, since it was reduced by 64% by a point mutation in the beta 3 cytoplasmic tail (S752-->P) that disrupts integrin signaling. Moreover, this interaction is integrin subunit specific since it was not observed with the cytoplasmic tails of the alpha IIb, beta 1, or beta 2 subunits. beta 3-Endonexin fusion proteins bound selectively to detergent-solubilized beta 3 from platelets and human umbilical vein endothelial cells, and beta 3-endonexin mRNA and protein were detected in platelets and other tissues. A related mRNA encoded a larger polypeptide that failed to bind to beta integrin tails. The apparent specificity of beta 3-endonexin for the beta 3 integrin subunit suggests potential mechanisms for selective modulation of integrin functions.
Shattil
S J
SJ
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
O'Toole
T
T
Eigenthaler
M
M
Thon
V
V
Williams
M
M
Babior
B M
BM
Ginsberg
M H
MH
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D016023:Integrins / Q000378:metabolism* / Q000648:ultrastructure; D008875:Middle Aged; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010455:Peptides / Q000032:analysis; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012680:Sensitivity and Specificity
C403295:ITGB3BP protein, human; D016023:Integrins; D009687:Nuclear Proteins; D010455:Peptides; D011506:Proteins; D012333:RNA, Messenger