The N-terminal domains of talin cooperate with the phosphotyrosine binding-like domain to activate β1 and β3 integrins

被引:110
|
作者
Bouaouina, Mohamed
Lad, Yatish
Calderwood, David A.
机构
[1] Yale Univ, Dept Pharmacol, New Haven, CT 06520 USA
[2] Yale Univ, Interdept Program Vasc Biol & Transplantat, New Haven, CT 06520 USA
关键词
D O I
10.1074/jbc.M709527200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The activation of integrin adhesion receptors from low to high affinity in response to intracellular cues controls cell adhesion and signaling. Binding of the cytoskeletal protein talin to the beta 3 integrin cytoplasmic tail is required for beta 3 activation, and the integrin-binding PTB-like F3 domain of talin is sufficient to activate beta 3 integrins. Here we report that, whereas the conserved talin-integrin interaction is also required for beta 1 activation, and talin F3 binds beta 1 and beta 3 integrins with comparable affinity, expression of the talin F3 domain is not sufficient to activate beta 1 integrins. beta 1 integrin activation could, however, be detected following expression of larger talin fragments that included the N-terminal and F1 domains, and mutagenesis indicates that these domains cooperate with talin F3 to mediate beta 1 activation. This effect is not due to increased affinity for the integrin beta tail and we hypothesize that the N-terminal domains function by targeting or orienting talin in such a way as to optimize the interaction with the integrin tail. Analysis of beta 3 integrin activation indicates that inclusion of the N-terminal and F1 domains also enhances F3-mediated beta 3 activation. Our results therefore reveal a role for the N-terminal and F1 domains of talin during integrin activation and highlight differences in talin-mediated activation of beta 1 and beta 3 integrins.
引用
收藏
页码:6118 / 6125
页数:8
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