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, A. Keith Stewart

Research output: Contribution to journalArticle

31 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Zhu, Y. X., Benn, S., Li, Z. H., Wei, E., Masih-Khan, E., Trieu, Y., Bali, M., McGlade, C. J., Claudio, J. O., & Stewart, A. K. (2004). The SH3-SAM adaptor HACS1 is up-regulated in B cell activation signaling cascades. Journal of Experimental Medicine, 200(6), 737-747. https://doi.org/10.1084/jem.20031816