The integrin LFA-1 signals through ZAP-70 to regulate expression of high-affinity LFA-1 on T lymphocytes.
Blood
; 117(12): 3331-42, 2011 Mar 24.
Article
em En
| MEDLINE
| ID: mdl-21200022
ABSTRACT
The integrin lymphocyte function-associated antigen 1 (LFA-1) controls many functions of T lymphocytes and is particularly essential during lymphocyte migration from blood into tissues. LFA-1 is considered to initiate "outside-in" signaling when bound to ligand intercellular adhesion molecule 1 (ICAM-1), but little is known about the proteins involved or where in the cell such LFA-1-mediated signaling might be operating. Here we show that LFA-1 is constitutively associated with the protein tyrosine kinases Lck and zeta chain-associated protein of 70 kDa (ZAP-70). When LFA-1 binds ICAM-1, both kinases become phosphorylated and the consequence of kinase activation is the conversion of intermediate- to high-affinity LFA-1 and an increase in close contact with ICAM-1. In the polarized T lymphocyte, phospho-ZAP-70 is concentrated within a region of high-affinity LFA-1 that includes talin and encompasses the lamella/lamellipodial interface as well as further back in the cell. Deficiency of ZAP-70 through inhibition or knockdown in T lymphocytes decreases the speed of migration on ICAM-1, as well as reducing firm adhesion under shear-flow conditions. Through its control of high-affinity LFA-1, the LFA-1/Lck/ZAP-70 complex is in position to initiate the rapid adhesion strengthening and migration necessary for T-lymphocyte responses when stimulated vasculature is encountered at sites of infection or injury.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Antígeno-1 Associado à Função Linfocitária
/
Proteína-Tirosina Quinase ZAP-70
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article