INTEGRIN BETA-3 CYTOPLASMIC TAIL IS NECESSARY AND SUFFICIENT FOR REGULATION OF ALPHA(5)BETA(1) PHAGOCYTOSIS BY ALPHA(V)BETA(3) AND INTEGRIN-ASSOCIATED PROTEIN

被引:100
作者
BLYSTONE, SD
LINDBERG, FP
LAFLAMME, SE
BROWN, EJ
机构
[1] WASHINGTON UNIV, SCH MED, DEPT MED, DIV INFECT DIS, ST LOUIS, MO 63110 USA
[2] ALBANY MED COLL, DEPT PHYSIOL & CELL BIOL, ALBANY, CA USA
关键词
D O I
10.1083/jcb.130.3.745
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Using a K562 cell transfection model, we have previously described a novel relationship between the integrins alpha(v) beta(3) and alpha(5) beta(1). alpha(v) beta(3) ligation was able to inhibit alpha(5) beta(1)-mediated phagocytosis without effect on alpha(5) beta(1)-mediated adhesion. The alpha(v) beta(3)-dependent inhibition apparently required a signal transduction cascade as it was reversed by inhibitors of serine/threonine kinases. Now, we have studied the mechanisms of signal transduction in this system and have found that the beta(3) cytoplasmic tail is both necessary and sufficient for initiation of the signal leading to inhibition of alpha(5) beta(1) phagocytosis. Ligation of integrin-associated protein (IAP), which has been implicated in alpha(v) beta(3) signal transduction, mimics the effects of alpha(v) beta(3) ligation only when the beta(3) integrin with an intact cytoplasmic tail is present. Although fibronectin-mediated phagocytosis requires the high affinity conformation of alpha(5) beta(1), ligation of alpha(v) beta(3)/IAP does not prevent acquisition of this high affinity state. We conclude that alpha(v) beta(3)/IAP ligation initates a signal transduction cascade, dependent upon the beta(3) cytoplasmic tail, which inhibits the phagocytic function of alpha(5) beta(1) at a step subsequent to modulation of integrin affinity.
引用
收藏
页码:745 / 754
页数:10
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