Phosphorylation-dependent regulation of T-cell activation by PAG/Cbp, a lipid raft-associated transmembrane adaptor

0191575 - UMG-J 20033078 RIV US eng J - Článek v odborném periodiku
Davidson, D. - Bakinowski, M. - Thomas, M. L. - Hořejší, Václav - Veillette, A.
Phosphorylation-dependent regulation of T-cell activation by PAG/Cbp, a lipid raft-associated transmembrane adaptor.
Molecular and Cellular Biology. Roč. 23, č. 6 (2003), s. 2017-2028. ISSN 0270-7306. E-ISSN 1098-5549
Grant CEP: GA MŠMT LN00A026
Výzkumný záměr: CEZ:AV0Z5052915
Klíčová slova: PAG * Csk * T cell activation
Kód oboru RIV: EC - Imunologie
Impakt faktor: 8.142, rok: 2003

PAG/Cbp is a transmembrane adaptor molecule found in lipid rafts, tyrosine phosphorylated and associated with Csk. PAG tyrosine phosphorylation and association with Csk are suppressed in response to activation of normal mouse T cells. By expressing wild-type and phosphorylation-defective (dominant-negative) PAG polypeptides in these cells, we found that the inhibitory effect of PAG is dependent on its capacity to be tyrosine phosphorylated and to associate with Csk. PAG-mediated inhibition was accompanied by a repression of proximal TCR signaling and was rescued by expression of a constitutively activated Src-related kinase, implying that it is due to an inactivation of Src kinases by PAG-associated Csk. Transmembrane PTP CD45 seems to play an important role in PAG dephosphorylation. Thus, PAG is a bona fide negative regulator of T-cell activation as a result of its capacity to recruit Csk; its inhibitory function in T cells is suppressed by CD45.
Trvalý link: http://hdl.handle.net/11104/0087318