A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells

被引：16

作者：

Tomlinson M.G. ^{[1
,4
]}

Woods D.B. ^{[1
,5
]}

McMahon M. ^{[1
,6
]}

Wahl M.I. ^{[2
]}

Witte O.N. ^{[2
]}

Kurosaki T. ^{[3
]}

Bolen J.B. ^{[1
,6
]}

Johnston J.A. ^{[1
,7
]}

机构：

[1] DNAX Res. Inst. Molec./Cell. Biology, Palo Alto

[2] Howard Hughes Medical Institute, Dept. Microbiol. Immunol./Molec. Gen, Univ. of California at Los Angeles, Los Angeles

[3] Department of Molecular Genetics, Kansai Medical University, Moriguchi 570

[4] Howard Hughes Medical Institute, Univ. of California at San Francisco, San Francisco, CA 94143, Third and Parnassus Ave.

[5] National Cancer Institute-FCRDC, Frederick, MD 21702-1201, P.O. Box B

[6] Cancer Research Institute, UCSF, Mt. Zion Cancer Center, San Francisco, CA 94115

[7] Department of Immunology, Queen's University Belfast, Belfast BT9 7BL

来源：

BMC Immunology | / 2卷 / 1期

关键词：

Estrogen Receptor; DT40 Cell; Calcium Mobilization; Estrogen Receptor Activation; Calcium Store Depletion;

D O I：

10.1186/1471-2172-2-4

中图分类号：

学科分类号：

摘要：

Background: Bruton's tyrosine kinase (Btk) is essential for B cell development and function. Mutations of Btk elicit X-linked agammaglobulinemia in humans and X-linked immunodeficiency in the mouse. Btk has been proposed to participate in B cell antigen receptor-induced signaling events leading to activation of phospholipase C-γ2 (PLCγ2) and calcium mobilization. However it is unclear whether Btk activation is alone sufficient for these signaling events, and whether Btk can activate additional pathways that do not involve PLCγ2. To address such issues we have generated Btk:ER, a conditionally active form of the kinase, and expressed it in the PLCγ2-deficient DT40 B cell line. Results: Activation of Btk:ER was sufficient to induce multiple B cell signaling pathways in PLCγ 2-sufficient DT40 cells. These included tyrosine phosphorylation of PLCγ2, mobilization of intracellular calcium, activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways, and apoptosis. In DT40 B cells deficient for PLCγ 2, Btk:ER activation failed to induce the signaling events described above with the consequence that the cells failed to undergo apoptosis. Conclusions: These data suggest that Btk:ER regulates downstream signaling pathways primarily via PLCγ2 in B cells. While it is not known whether activated Btk:ER precisely mimics activated Btk, this conditional system will likely facilitate the dissection of the role of Btk and its family members in a variety of biological processes in many different cell types. © 2001 Tomlinson et al, licensee BioMed Central Ltd.

引用

共 44 条

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