The SH3-SAM adaptor HACS1 is up-regulated in B cell activation signaling cascades

Yuan Xiao Zhu, Sally Benn, Zhi Hua Li, Ellen Wei, Esther Masih-Khan, Young Trieu, Meenakshi Bali, C. Jane McGlade, Jaime O. Claudio, Alexander Keith Stewart

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

HACS1 is a Src homology 3 and sterile alpha motif domain-containing adaptor that is preferentially expressed in normal hematopoietic tissues and malignancies including myeloid leukemia, lymphoma, and myeloma. Microarray data showed HACS1 expression is up-regulated in activated human B cells treated with interleukin (IL)-4, CD40L, and anti-immunoglobulin (Ig)M and clustered with genes involved in signaling, including TNF receptor-associated protein 1, signaling lymphocytic activation molecule, IL-6, and DEC205. Immunoblot analysis demonstrated that HACS1 is up-regulated by IL-4, IL-13, anti-IgM, and anti-CD40 in human peripheral blood B cells. In murine spleen B cells, Hacs1 can also be up-regulated by lipopolysaccharide but not IL-13. Induction of Hacs1 by IL-4 is dependent on Stat6 signaling and can also be impaired by inhibitors of phosphatidylinositol 3-kinase, protein kinase C, and nuclear factor κB. HACS1 associates with tyrosine-phosphorylated proteins after B cell activation and binds in vitro to the inhibitory molecule paired Ig-like receptor B. Overexpression of HACS1 in murine spleen B cells resulted in a down-regulation of the activation marker CD23 and enhancement of CD138 expression, IgM secretion, and Xbp-1 expression. Knock down of HACS1 in a human B lymphoma cell line by small interfering ribonucleic acid did not significantly change IL-4-stimulated B cell proliferation. Our study demonstrates that HACS1 is up-regulated by B cell activation signals and is a participant in B cell activation and differentiation.

Original languageEnglish (US)
Pages (from-to)737-747
Number of pages11
JournalJournal of Experimental Medicine
Volume200
Issue number6
DOIs
StatePublished - Sep 20 2004
Externally publishedYes

Fingerprint

B-Lymphocytes
Interleukin-4
Interleukin-13
Immunoglobulin M
Lymphoma
TNF Receptor-Associated Factor 1
Spleen
Phosphatidylinositol 3-Kinase
CD40 Ligand
Myeloid Leukemia
Hematologic Neoplasms
Protein Kinase C
Tyrosine
Lipopolysaccharides
Immunoglobulins
Cell Differentiation
Interleukin-6
Blood Cells
Down-Regulation
Cell Proliferation

Keywords

  • Adaptor protein
  • B lymphocytes
  • Gene expression
  • Interleukin-4
  • Signaling

ASJC Scopus subject areas

  • Immunology

Cite this

The SH3-SAM adaptor HACS1 is up-regulated in B cell activation signaling cascades. / Zhu, Yuan Xiao; Benn, Sally; Li, Zhi Hua; Wei, Ellen; Masih-Khan, Esther; Trieu, Young; Bali, Meenakshi; McGlade, C. Jane; Claudio, Jaime O.; Stewart, Alexander Keith.

In: Journal of Experimental Medicine, Vol. 200, No. 6, 20.09.2004, p. 737-747.

Research output: Contribution to journalArticle

Zhu, YX, Benn, S, Li, ZH, Wei, E, Masih-Khan, E, Trieu, Y, Bali, M, McGlade, CJ, Claudio, JO & Stewart, AK 2004, 'The SH3-SAM adaptor HACS1 is up-regulated in B cell activation signaling cascades', Journal of Experimental Medicine, vol. 200, no. 6, pp. 737-747. https://doi.org/10.1084/jem.20031816
Zhu, Yuan Xiao ; Benn, Sally ; Li, Zhi Hua ; Wei, Ellen ; Masih-Khan, Esther ; Trieu, Young ; Bali, Meenakshi ; McGlade, C. Jane ; Claudio, Jaime O. ; Stewart, Alexander Keith. / The SH3-SAM adaptor HACS1 is up-regulated in B cell activation signaling cascades. In: Journal of Experimental Medicine. 2004 ; Vol. 200, No. 6. pp. 737-747.
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AU - Benn, Sally

AU - Li, Zhi Hua

AU - Wei, Ellen

AU - Masih-Khan, Esther

AU - Trieu, Young

AU - Bali, Meenakshi

AU - McGlade, C. Jane

AU - Claudio, Jaime O.

AU - Stewart, Alexander Keith

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