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SOCS3 protein developmentally regulates the chemokine receptor CXCR4-FAK signaling pathway during B lymphopoiesis.

Authors
  • Le, Yi
  • Zhu, Bing-Mei
  • Harley, Brendan
  • Park, Shin-Young
  • Kobayashi, Takashi
  • Manis, John P
  • Luo, Hongbo R
  • Yoshimura, Akihiko
  • Hennighausen, Lothar
  • Silberstein, Leslie E
Type
Published Article
Journal
Immunity
Publisher
Elsevier
Publication Date
Nov 01, 2007
Volume
27
Issue
5
Pages
811–823
Identifiers
PMID: 18031698
Source
Medline
License
Unknown

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 Cre(MMTV)Socs3(fl/fl) mice exhibited prolonged FAK phosphorylation and adhesion to VCAM-1. In contrast to wild-type mice, Cre(MMTV)Socs3(fl/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.

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