The B-cell transmembrane protein CD72 binds to and is an in vivo substrate of the protein tyrosine phosphatase SHP-1.
Curr Biol
; 8(18): 1009-17, 1998 Sep 10.
Article
en En
| MEDLINE
| ID: mdl-9740800
ABSTRACT
BACKGROUND:
Signals from the B-cell antigen receptor (BCR) help to determine B-cell fate, directing either proliferation, differentiation, or growth arrest/apoptosis. The protein tyrosine phosphatase SHP-1 is known to regulate the strength of BCR signaling. Although the B-cell co-receptor CD22 binds SHP-1, B cells in CD22-deficient mice are much less severely affected than those in SHP-1-deficient mice, suggesting that SHP-1 may also regulate B-cell signaling by affecting other signaling molecules. Moreover, direct substrates of SHP-1 have not been identified in any B-cell signaling pathway.RESULTS:
We identified the B-cell transmembrane protein CD72 as a new SHP-1 binding protein and as an in vivo substrate of SHP-1 in B cells. We also defined the binding sites for SHP-1 and the adaptor protein Grb2 on CD72. Tyrosine phosphorylation of CD72 correlated strongly with BCR-induced growth arrest/apoptosis in B-cell lines and in primary B cells. Preligation of CD72 attenuated BCR-induced growth arrest/death signals in immature and mature B cells or B-cell lines, whereas preligation of CD22 enhanced BCR-induced growth arrest/apoptosis.CONCLUSIONS:
We have identified CD72 as the first clear in vivo substrate of SHP-1 in B cells. Our results suggest that tyrosine-phosphorylated CD72 may transmit signals for BCR-induced apoptosis. By dephosphorylation CD72. SHP-1 may have a positive role in B-cell signaling. These results have potentially important implications for the involvement of CD72 and SHP-1 in B-cell development and autoimmunity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Receptores de Antígenos de Linfocitos B
/
Antígenos de Diferenciación de Linfocitos B
/
Antígenos CD
/
Proteínas Tirosina Fosfatasas
Límite:
Animals
Idioma:
En
Revista:
Curr Biol
Asunto de la revista:
BIOLOGIA
Año:
1998
Tipo del documento:
Article
País de afiliación:
Canadá