Nore1B regulates TCR signaling via Ras and Carma1.

Abstract:

:Nore1A was originally identified as a potential Ras effector, and Nore1B is an alternatively spliced isoform. Both share a Ras/Rap association domain (RA domain) but only Nore1A contains sequence motifs that predict SH3 domain binding and diacylglycerol/phorbol ester binding in the amino-terminal region. Here we report that Carma1 binds to Nore1A and Nore1B through the RA domain and that Carma1 interacts with active Ras in the presence of Nore1B. RNA interference against Nore1B attenuates NF-kappaB activation induced by T cell receptor (TCR) ligation, but not NF-kappaB activation induced by TNFalpha or lipoteichoic acid. In addition, Nore1B is also required for KiRas GV12-mediated ERK1 activation and Elk1 reporter activity in T cells. We also provide evidence that knockdown of Nore1B also impairs polarized redistribution of Ras at the B cell-T cell immune interface. Together, these findings suggest that endogenous Nore1B recruits active Ras to the APC-T cell interface and mediates the interaction between Ras and Carma1.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Ishiguro K,Avruch J,Landry A,Qin S,Ando T,Goto H,Xavier R

doi

10.1016/j.cellsig.2006.01.015

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

1647-54

issue

10

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(06)00019-2

journal_volume

18

pub_type

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