Blystone S D, Williams M P, Slater S E, Brown E J
Department of Medicine, Infectious Diseases Division, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Biol Chem. 1997 Nov 7;272(45):28757-61. doi: 10.1074/jbc.272.45.28757.
Leukocytes and platelets require stimulation for optimal beta3 integrin receptor function, whereas beta3 function is constitutive in many other cells. The molecular mechanisms that enhance integrin function in stimulated hematopoietic cells are poorly understood. Phosphorylation of the beta3 cytoplasmic tail is a recently described but prevalent phenomenon, with unknown effects on alphavbeta3 function. Here, we show that mutation of the beta3 cytoplasmic tail tyrosine 747 to phenylalanine (Y747F) prevents beta3 tyrosine phosphorylation in two cell lines. Whereas this mutation has no effect on alphavbeta3-mediated adhesion in a cell with constitutive beta3 function, it completely abolishes adhesion and clot retraction by a cell that requires stimulation for beta3 function. Ligand-induced conformational change as detected by LIBS-1 antibody occurs normally in Y747F mutant alphavbeta3. Thus, tyrosine 747 of beta3 is required for stimulation of alphavbeta3-mediated adhesion, probably due to its phosphorylation. Because the motif in beta3 required for tyrosine phosphorylation is shared by several integrin beta-chains, this may be a conserved mechanism for regulation of integrin-dependent adhesion.
白细胞和血小板需要刺激才能实现最佳的β3整合素受体功能，而β3功能在许多其他细胞中是组成性的。在受刺激的造血细胞中增强整合素功能的分子机制尚不清楚。β3细胞质尾部的磷酸化是最近描述的一种普遍现象，对αvβ3功能的影响尚不清楚。在这里，我们表明，将β3细胞质尾部酪氨酸747突变为苯丙氨酸（Y747F）可阻止两种细胞系中的β3酪氨酸磷酸化。虽然这种突变对具有组成性β3功能的细胞中αvβ3介导的黏附没有影响，但它完全消除了需要刺激才能实现β3功能细胞的黏附和凝块收缩。LIBS-1抗体检测到的配体诱导的构象变化在Y747F突变体αvβ3中正常发生。因此，β3的酪氨酸747是刺激αvβ3介导的黏附所必需的，可能是由于其磷酸化。由于几种整合素β链共享β3中酪氨酸磷酸化所需的基序，这可能是调节整合素依赖性黏附的一种保守机制。
