RECRUITMENT AND ACTIVATION OF PTP1C IN NEGATIVE REGULATION OF ANTIGENRECEPTOR SIGNALING BY FC-GAMMA-RIIB1

Coligation of the Fc receptor on B cells, Fc gamma RIIB1, with the B c ell antigen receptor (BCR) leads to abortive BCR signaling. Here it wa s shown that the Fc gamma RIIB1 recruits the phosphotyrosine phosphata se PTP1C after BCR coligation. This association is mediated by the bin ding of a 13-amino acid tyrosine-phosphorylated sequence to the carbox yl terminal Src homology 2 domain of PTP1C and activates PTP1C. Inhibi tory signaling and PTP1C recruitment are dependent on the presence of the tyrosine within the 13-amino acid sequence. Inhibitory signaling m ediated by Fc gamma RIIB1 is deficient in motheaten mice which do not express functional PTP1C. Thus, PTP1C is an effector of BCR-Fc gamma R IIB1 negative signal cooperativity.