Recruitment and activation of PTP1C in negative regulation of antigen receptor signaling by Fc gamma RIIB1.
Coligation of the Fc receptor on B cells, Fc gamma RIIB1, with the B cell antigen receptor (BCR) leads to abortive BCR signaling. Here it was shown that the Fc gamma RIIB1 recruits the phosphotyrosine phosphatase PTP1C after BCR coligation. This association is mediated by the binding of a 13-amino acid tyrosine-phosphorylated sequence to the carboxyl-terminal Src homology 2 domain of PTP1C and activates PTP1C. Inhibitory signaling and PTP1C recruitment are dependent on the presence of the tyrosine within the 13-amino acid sequence. Inhibitory signaling mediated by Fc gamma RIIB1 is deficient in motheaten mice which do not express functional PTP1C. Thus, PTP1C is an effector of BCR-Fc gamma RIIB1 negative signal cooperativity.
D'Ambrosio
D
D
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Hippen
K L
KL
Minskoff
S A
SA
Mellman
I
I
Pani
G
G
Siminovitch
K A
KA
Cambier
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D002118:Calcium