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

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.
Mesh Terms:
Animals, B-Lymphocytes, Cell Adhesion, Flow Cytometry, Fluorescent Antibody Technique, Focal Adhesion Kinase 1, Humans, Immunoblotting, Immunohistochemistry, Immunoprecipitation, Lymphopoiesis, Mice, Phosphorylation, Precursor Cells, B-Lymphoid, Receptors, CXCR4, Signal Transduction, Suppressor of Cytokine Signaling Proteins, Transfection, Ubiquitination, Vascular Cell Adhesion Molecule-1
Immunity
Date: Nov. 01, 2007
Download Curated Data For This Publication
122737
Switch View:
  • Interactions 2
  • PTM Genes 2