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SLP-76 is recruited to CD22 and dephosphorylated by SHP-1, thereby regulating B cell receptor-induced c-Jun N-terminal kinase activation.
Eur J Immunol. 2005 Feb; 35(2):644-54.EJ

Abstract

Despite the important role in the development and activation of T cells, NK cells, mast cells, and macrophages, the expression and function of SLP-76 in B cells have been largely unknown. Here we demonstrate that SLP-76 is expressed in all mouse B cell lines tested and in normal splenic B cells, and serves as an SHP-1 substrate. Dephosphorylation of SLP-76 by SHP-1 inhibits its association with Nck, down-regulating c-Jun N-terminal kinase (JNK) activation and exerting a positive effect on apoptosis. Knockdown of SLP-76 in WEHI-231 cells by small interfering RNA attenuated JNK activation, but showed little effects on extracellular signal-regulated kinase (ERK) or p38 activation. Although WEHI-231 does not express linker for activation of T cells (LAT), SLP-76 localizes in membrane fraction, which increases following B cell receptor (BCR) cross-linking. Further analyses revealed that SLP-76 complexed with Gads is associated with tyrosine-phosphorylated CD22 through the SH2 domains of SLP-76 and Gads. Given that SHP-1 binds to CD22 upon BCR ligation, our findings suggest that dephosphorylation of SLP-76 recruited to CD22 by SHP-1 inhibits BCR-induced JNK activation, dictating apoptosis.

Authors+Show Affiliations

Department of Immunology and Signal Transduction, Tokyo Metropolitan Institute for Neuroscience, Tokyo Metropolitan Organization for Medical Research, Tokyo, Japan. kzmizuno@tmin.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15668918

Citation

Mizuno, Kazuya, et al. "SLP-76 Is Recruited to CD22 and Dephosphorylated By SHP-1, Thereby Regulating B Cell Receptor-induced c-Jun N-terminal Kinase Activation." European Journal of Immunology, vol. 35, no. 2, 2005, pp. 644-54.
Mizuno K, Tagawa Y, Watanabe N, et al. SLP-76 is recruited to CD22 and dephosphorylated by SHP-1, thereby regulating B cell receptor-induced c-Jun N-terminal kinase activation. Eur J Immunol. 2005;35(2):644-54.
Mizuno, K., Tagawa, Y., Watanabe, N., Ogimoto, M., & Yakura, H. (2005). SLP-76 is recruited to CD22 and dephosphorylated by SHP-1, thereby regulating B cell receptor-induced c-Jun N-terminal kinase activation. European Journal of Immunology, 35(2), 644-54.
Mizuno K, et al. SLP-76 Is Recruited to CD22 and Dephosphorylated By SHP-1, Thereby Regulating B Cell Receptor-induced c-Jun N-terminal Kinase Activation. Eur J Immunol. 2005;35(2):644-54. PubMed PMID: 15668918.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SLP-76 is recruited to CD22 and dephosphorylated by SHP-1, thereby regulating B cell receptor-induced c-Jun N-terminal kinase activation. AU - Mizuno,Kazuya, AU - Tagawa,Yuko, AU - Watanabe,Noriyuki, AU - Ogimoto,Mami, AU - Yakura,Hidetaka, PY - 2005/1/26/pubmed PY - 2005/3/30/medline PY - 2005/1/26/entrez SP - 644 EP - 54 JF - European journal of immunology JO - Eur J Immunol VL - 35 IS - 2 N2 - Despite the important role in the development and activation of T cells, NK cells, mast cells, and macrophages, the expression and function of SLP-76 in B cells have been largely unknown. Here we demonstrate that SLP-76 is expressed in all mouse B cell lines tested and in normal splenic B cells, and serves as an SHP-1 substrate. Dephosphorylation of SLP-76 by SHP-1 inhibits its association with Nck, down-regulating c-Jun N-terminal kinase (JNK) activation and exerting a positive effect on apoptosis. Knockdown of SLP-76 in WEHI-231 cells by small interfering RNA attenuated JNK activation, but showed little effects on extracellular signal-regulated kinase (ERK) or p38 activation. Although WEHI-231 does not express linker for activation of T cells (LAT), SLP-76 localizes in membrane fraction, which increases following B cell receptor (BCR) cross-linking. Further analyses revealed that SLP-76 complexed with Gads is associated with tyrosine-phosphorylated CD22 through the SH2 domains of SLP-76 and Gads. Given that SHP-1 binds to CD22 upon BCR ligation, our findings suggest that dephosphorylation of SLP-76 recruited to CD22 by SHP-1 inhibits BCR-induced JNK activation, dictating apoptosis. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/15668918/SLP_76_is_recruited_to_CD22_and_dephosphorylated_by_SHP_1_thereby_regulating_B_cell_receptor_induced_c_Jun_N_terminal_kinase_activation_ L2 - https://doi.org/10.1002/eji.200425465 DB - PRIME DP - Unbound Medicine ER -