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Original Article

^a Department of Microbiology, University of Washington, Seattle, Washington 98195
^b Department of Immunology, University of Washington, Seattle, Washington 98195
^c Department of Pathology, University of Washington, Seattle, Washington 98195
^d Regional Primate Research Center, University of Washington, Seattle, Washington 98195
Department of Microbiology, University of Washington, Seattle, WA 98195.206-543-8297206-543-7414

aaronn{at}u.washington.edu

We have identified and characterized a novel src homology 2 (SH2) and pleckstrin homology (PH) domain–containing adaptor protein, designated Bam32 (for B cell adaptor molecule of 32 kD). cDNAs encoding the human and mouse Bam32 coding sequences were isolated and the human bam32 gene was mapped to chromosome 4q25–q27. Bam32 is expressed by B lymphocytes, but not T lymphocytes or nonhematopoietic cells. Human germinal center B cells show increased Bam32 expression, and resting B cells rapidly upregulate expression of Bam32 after ligation of CD40, but not immunoglobulin M. Bam32 is tyrosine-phosphorylated upon B cell antigen receptor (BCR) ligation or pervanadate stimulation and associates with phospholipase C2. After BCR ligation, Bam32 is recruited to the plasma membrane through its PH domain. Membrane recruitment requires phosphatidylinositol 3-kinase (PI3K) activity and an intact PI(3,4,5)P₃-binding motif, suggesting that membrane association occurs through binding to 3-phosphoinositides. Expression of Bam32 in B cells leads to a dose-dependent inhibition of BCR-induced activation of nuclear factor of activated T cells (NF-AT), which is blocked by deletion of the PH domain or mutation of the PI(3,4,5)P₃-binding motif. Thus, Bam32 represents a novel B cell–associated adaptor that regulates BCR signaling downstream of PI3K.

Key Words: immunoglobulin • germinal center • signal transduction • SH2 domain • pleckstrin homology domain

Abbreviations used in this paper: Bam32, B cell adaptor molecule of 32 kD; BCR, B cell antigen receptor; BLNK, B cell linker; Btk, Bruton's tyrosine kinase; EGFP, enhanced green fluorescent protein; FDC, follicular dendritic cell; FISH, fluorescence in situ hybridization; G3PDH, glyceraldehyde 3-phosphate dehydrogenase; GC, germinal center; GST, glutathione S-transferase; NF-AT, nuclear factor of activated T cells; NF-B, nuclear factor of binding; PdBu, phorbol-12,13-dibutyrate; PH, pleckstrin homology; PI, phosphatidylinositol; PI3K, phosphatidylinositol 3-kinase; PLC, phospholipase C; PTK, protein tyrosine kinase; RACE, rapid amplification of cDNA ends; RT, reverse transcription; SH2, src homology 2; SSH, suppression subtractive hybridization.

© 2000 The Rockefeller University Press

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This article has been cited by other articles:

• Costantini, J. L., Cheung, S. M. S., Hou, S., Li, H., Kung, S. K., Johnston, J. B., Wilkins, J. A., Gibson, S. B., Marshall, A. J. (2009). TAPP2 links phosphoinositide 3-kinase signaling to B-cell adhesion through interaction with the cytoskeletal protein utrophin: expression of a novel cell adhesion-promoting complex in B-cell leukemia. Blood 114: 4703-4712 [Abstract] [Full Text]  

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