A crucial role for the p110δ subunit of phosphatidylinositol 3-kinase in B cell development and activation

被引：369

作者：

Clayton, E

Bardi, G

Bell, SE

Chantry, D

Downes, CP

Gray, A

Humphries, LA

Rawlings, D

Reynolds, H

Vigorito, E

Turner, M ^{[1
]}

机构：

[1] Babraham Inst, Mol Immunol Programme, Lab Lymphocyte Signaling & Dev, Cambridge CB2 4AT, England

[2] COS Corp, Bothell, WA 98021 USA

[3] Univ Dundee, Dept Biochem, Dundee DD1 5EH, Scotland

[4] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA

[5] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA

[6] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2002年 / 196卷 / 06期

关键词：

Akt; Btk; calcium; gone targeting; p110; delta;

D O I：

10.1084/jem.20020805

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Mice lacking the p 1108 catalytic subunit of phosphatidylinositol 3-kinase have reduced numbers of B1 and marginal zone B cells, reduced levels of serum immunoglobulins, respond poorly to immunization with type II thymus-independent antigen, and are defective in their primary and secondary responses to thymus-dependent antigen. p110delta(-/-) B cells proliferate poorly in response to B cell receptor (BCR) or CD40 signals in vitro, fail to activate protein kinase B, and are prone to apoptosis. p110delta function is required for BCR-mediated calcium flux, activation of phosphipaseCgamma2, and Bruton's tyrosine kinase. Thus, p110delta plays a critical role in B cell homeostasis and function.

引用

页码：753 / 763

页数：11

共 63 条

[1] BLNK mediates Syk-dependent Btk activation
Baba, Y
Hashimoto, S
Matsushita, M
Watanabe, D
Kishimoto, T
Kurosaki, T
Tsukada, S
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (05) : 2582 - 2586
[2] Activation of phospholipase C-γ by phosphatidylinositol 3,4,5-trisphosphate
Bae, YS
Cantley, LG
Chen, CS
Kim, SR
Kwon, KS
Rhee, SG
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (08) : 4465 - 4469
[3] Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110α subunit of phosphoinositide 3-kinase
Bi, L
Okabe, I
Bernard, DJ
Wynshaw-Boris, A
Nussbaum, RL
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (16) : 10963 - 10968
[4] Early embryonic lethality in mice deficient in the p110β catalytic subunit of PI 3-kinase
Bi, L
Okabe, I
Bernard, DJ
Nussbaum, RL
[J]. MAMMALIAN GENOME, 2002, 13 (03) : 169 - 172
[5] SHIP modulates immune receptor responses by regulating membrane association of Btk
Bolland, S
Pearse, RN
Kurosaki, T
Ravetch, JV
[J]. IMMUNITY, 1998, 8 (04) : 509 - 516
[6] Antigen-receptor cross-linking and lipopolysaccharide trigger distinct phosphoinositide 3-kinase-dependent pathways to NF-κB activation in primary B cells
Bone, H
Williams, NA
[J]. INTERNATIONAL IMMUNOLOGY, 2001, 13 (06) : 807 - 816
[7] Differential regulation of B cell development, activation, and death by the Src homology 2 domain-containing 5′ inositol phosphatase (SHIP)
Brauweiler, A
Tamir, I
Dal Porto, J
Benschop, RJ
Helgason, CD
Humphries, RK
Freed, JH
Cambier, JC
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (09) : 1545 - 1554
[8] Buhl AM, 1999, J IMMUNOL, V162, P4438
[9] Qualitative regulation of B cell antigen receptor signaling by CD19: Selective requirement for PI3-kinase activation, inositol-1,4,5-trisphosphate production and Ca2+ mobilization
Buhl, AM
Pleiman, CM
Rickert, RC
Cambier, JC
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (11) : 1897 - 1910
[10] p110 delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes
Chantry, D
Vojtek, A
Kashishian, A
Holtzman, DA
Wood, C
Gray, PW
Cooper, JA
Hoekstra, MF
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (31) : 19236 - 19241

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