Cargando…
B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1
The B cell adaptor containing src homology 2 domain (BASH; also termed BLNK or SLP-65), is crucial for B cell antigen receptor (BCR)-mediated activation, proliferation, and differentiation of B cells. BCR-mediated tyrosine-phosphorylation of BASH creates binding sites for signaling effectors such as...
Autores principales: | , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2001
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193495/ https://www.ncbi.nlm.nih.gov/pubmed/11514608 |
_version_ | 1782147484303228928 |
---|---|
author | Tsuji, Sachiyo Okamoto, Mariko Yamada, Koichi Okamoto, Noriaki Goitsuka, Ryo Arnold, Rudiger Kiefer, Friedemann Kitamura, Daisuke |
author_facet | Tsuji, Sachiyo Okamoto, Mariko Yamada, Koichi Okamoto, Noriaki Goitsuka, Ryo Arnold, Rudiger Kiefer, Friedemann Kitamura, Daisuke |
author_sort | Tsuji, Sachiyo |
collection | PubMed |
description | The B cell adaptor containing src homology 2 domain (BASH; also termed BLNK or SLP-65), is crucial for B cell antigen receptor (BCR)-mediated activation, proliferation, and differentiation of B cells. BCR-mediated tyrosine-phosphorylation of BASH creates binding sites for signaling effectors such as phospholipase Cγ (PLCγ)2 and Vav, while the function of its COOH-terminal src homology 2 domain is unknown. We have now identified hematopoietic progenitor kinase (HPK)1, a STE20-related serine/threonine kinase, as a protein that inducibly interacts with the BASH SH2 domain. BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation. Furthermore, HPK1 augmented, whereas its kinase-dead mutant inhibited IκB kinase β (IKKβ) activation by BCR engagement. These results reveal a novel BCR signaling pathway leading to the activation of HPK1 and subsequently IKKβ, in which BASH recruits tyrosine-phosphorylated HPK1 into the BCR signaling complex. |
format | Text |
id | pubmed-2193495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21934952008-04-14 B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1 Tsuji, Sachiyo Okamoto, Mariko Yamada, Koichi Okamoto, Noriaki Goitsuka, Ryo Arnold, Rudiger Kiefer, Friedemann Kitamura, Daisuke J Exp Med Original Article The B cell adaptor containing src homology 2 domain (BASH; also termed BLNK or SLP-65), is crucial for B cell antigen receptor (BCR)-mediated activation, proliferation, and differentiation of B cells. BCR-mediated tyrosine-phosphorylation of BASH creates binding sites for signaling effectors such as phospholipase Cγ (PLCγ)2 and Vav, while the function of its COOH-terminal src homology 2 domain is unknown. We have now identified hematopoietic progenitor kinase (HPK)1, a STE20-related serine/threonine kinase, as a protein that inducibly interacts with the BASH SH2 domain. BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. BCR-mediated activation of HPK1 was impaired in Syk- or BASH-deficient B cells. The functional SH2 domain of BASH and Tyr-379 within HPK1 which we identified as a Syk-phosphorylation site were both necessary for interaction of both proteins and efficient HPK1 activation after BCR stimulation. Furthermore, HPK1 augmented, whereas its kinase-dead mutant inhibited IκB kinase β (IKKβ) activation by BCR engagement. These results reveal a novel BCR signaling pathway leading to the activation of HPK1 and subsequently IKKβ, in which BASH recruits tyrosine-phosphorylated HPK1 into the BCR signaling complex. The Rockefeller University Press 2001-08-20 /pmc/articles/PMC2193495/ /pubmed/11514608 Text en © 2001 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Original Article Tsuji, Sachiyo Okamoto, Mariko Yamada, Koichi Okamoto, Noriaki Goitsuka, Ryo Arnold, Rudiger Kiefer, Friedemann Kitamura, Daisuke B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1 |
title | B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1 |
title_full | B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1 |
title_fullStr | B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1 |
title_full_unstemmed | B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1 |
title_short | B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1 |
title_sort | b cell adaptor containing src homology 2 domain (bash) links b cell receptor signaling to the activation of hematopoietic progenitor kinase 1 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193495/ https://www.ncbi.nlm.nih.gov/pubmed/11514608 |
work_keys_str_mv | AT tsujisachiyo bcelladaptorcontainingsrchomology2domainbashlinksbcellreceptorsignalingtotheactivationofhematopoieticprogenitorkinase1 AT okamotomariko bcelladaptorcontainingsrchomology2domainbashlinksbcellreceptorsignalingtotheactivationofhematopoieticprogenitorkinase1 AT yamadakoichi bcelladaptorcontainingsrchomology2domainbashlinksbcellreceptorsignalingtotheactivationofhematopoieticprogenitorkinase1 AT okamotonoriaki bcelladaptorcontainingsrchomology2domainbashlinksbcellreceptorsignalingtotheactivationofhematopoieticprogenitorkinase1 AT goitsukaryo bcelladaptorcontainingsrchomology2domainbashlinksbcellreceptorsignalingtotheactivationofhematopoieticprogenitorkinase1 AT arnoldrudiger bcelladaptorcontainingsrchomology2domainbashlinksbcellreceptorsignalingtotheactivationofhematopoieticprogenitorkinase1 AT kieferfriedemann bcelladaptorcontainingsrchomology2domainbashlinksbcellreceptorsignalingtotheactivationofhematopoieticprogenitorkinase1 AT kitamuradaisuke bcelladaptorcontainingsrchomology2domainbashlinksbcellreceptorsignalingtotheactivationofhematopoieticprogenitorkinase1 |