SOCS3 Protein Developmentally Regulates the Chemokine Receptor CXCR4-FAK Signaling Pathway during B Lymphopoiesis

Yi Le, Bing Mei Zhu, Brendan Harley, Shin Young Park, Takashi Kobayashi, John P. Manis, Hongbo R. Luo, Akihiko Yoshimura, Lothar Hennighausen, Leslie E. Silberstein

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

The chemokine CXCL12 induces prolonged focal adhesion kinase (FAK) phosphorylation and sustained proadhesive responses in progenitor bone-marrow (BM) B cells, but not in mature peripheral B cells. Here we demonstrate that suppressor of cytokine signaling 3 (SOCS3) regulated CXCL12-induced FAK phosphorylation through the ubiquitin-proteasome pathway. CXCL12 triggered increased FAK ubiquitination in mature B cells, but not in progenitor B cells. Accordingly, SOCS3 expression was low in progenitor B cells, increased in immature B cells, and highest in mature B cells. SOCS3 overexpression in pro-B cells impaired CXCL12-induced FAK phosphorylation and proadhesive responses. Conversely, SOCS3-deficient mature B cells from CreMMTVSocs3fl/fl mice exhibited prolonged FAK phosphorylation and adhesion to VCAM-1. In contrast to wild-type mice, CreMMTVSocs3fl/fl mice had a 2-fold increase in immature B cells, which were evenly distributed in endosteal and perisinusoidal BM compartments. We propose that the developmental regulation of CXCR4-FAK signaling by SOCS3 is an important mechanism to control the lodgement of B cell precursors in the BM microenvironment.

Original languageEnglish
Pages (from-to)811-823
Number of pages13
JournalImmunity
Volume27
Issue number5
DOIs
Publication statusPublished - 2007 Nov 26
Externally publishedYes

Keywords

  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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