| First Author | Zhang H | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 48 | Pages | 19323-8 |
| PubMed ID | 22084078 | Mgi Jnum | J:180397 |
| Mgi Id | MGI:5306200 | Doi | 10.1073/pnas.1108052108 |
| Citation | Zhang H, et al. (2011) Basic residues in the T-cell receptor zeta cytoplasmic domain mediate membrane association and modulate signaling. Proc Natl Acad Sci U S A 108(48):19323-8 |
| abstractText | The T-cell receptor (TCR) consists of a TCRalphabeta heterodimer, a TCRzeta homodimer, and CD3gammaepsilon and CD3deltaepsilon heterodimers. The precise mechanism of T-cell triggering following TCR ligand engagement remains elusive. Previous studies reported that the cytoplasmic tail of CD3epsilon binds to the plasma membrane through a basic residue-rich stretch (BRS) and proposed that dissociation from the membrane is required for phosphorylation thereof. In this report we show that BRS motifs within the cytoplasmic tail of TCRzeta mediate association with the plasma membrane and that TCR engagement results in TCRzeta dissociation from the membrane. This dissociation requires phosphorylation of the TCRzeta immunoreceptor tyrosine-based activation motifs by lymphocyte cell-specificprotein tyrosine kinase (Lck) but not zeta-chain-associated protein kinase 70 binding. Mutations of the TCRzeta BRS motifs that disrupt this membrane association attenuate proximal and distal responses induced by TCR engagement. These mutations appear to alter the localization of TCRzeta with respect to Lck as well as the mobility of the TCR complex. This study reveals that tyrosine phosphorylation of the TCRzeta cytoplasmic domain regulates its association with the plasma membrane and highlights the functional importance of TCRzeta BRS motifs. |
