TY - JOUR
T1 - SOCS3 Protein Developmentally Regulates the Chemokine Receptor CXCR4-FAK Signaling Pathway during B Lymphopoiesis
AU - Le, Yi
AU - Zhu, Bing Mei
AU - Harley, Brendan
AU - Park, Shin Young
AU - Kobayashi, Takashi
AU - Manis, John P.
AU - Luo, Hongbo R.
AU - Yoshimura, Akihiko
AU - Hennighausen, Lothar
AU - Silberstein, Leslie E.
N1 - Funding Information:
We thank M. Armant, M. St. Andre, and M. Cohen for their help in FACS analysis. We thank T. Bowman for preparing mouse BM sections. This work was supported by grants from the National Institutes of Health (HL56949 and HL074355).
PY - 2007/11/26
Y1 - 2007/11/26
N2 - 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.
AB - 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.
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=36048932040&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36048932040&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2007.09.011
DO - 10.1016/j.immuni.2007.09.011
M3 - Article
C2 - 18031698
AN - SCOPUS:36048932040
SN - 1074-7613
VL - 27
SP - 811
EP - 823
JO - Immunity
JF - Immunity
IS - 5
ER -
