[PDF][PDF] SOCS3 protein developmentally regulates the chemokine receptor CXCR4-FAK signaling pathway during B lymphopoiesis

Y Le, BM Zhu, B Harley, SY Park, T Kobayashi… - Immunity, 2007 - cell.com
Y Le, BM Zhu, B Harley, SY Park, T Kobayashi, JP Manis, HR Luo, A Yoshimura
Immunity, 2007cell.com
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 …
Summary
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.
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