Le, YiZhu, Bing-MeiHarley, BrendanPark, Shin-YoungKobayashi, TakashiManis, JohnLuo, HongboYoshimura, AkihikoHennighausen, LotharSilberstein, Leslie2014-11-042007Le, Yi, Bing-Mei Zhu, Brendan Harley, Shin-Young Park, Takashi Kobayashi, John P. Manis, Hongbo R. Luo, Akihiko Yoshimura, Lothar Hennighausen, and Leslie E. Silberstein. 2007. “SOCS3 Protein Developmentally Regulates the Chemokine Receptor CXCR4-FAK Signaling Pathway during B Lymphopoiesis.” Immunity 27 (5) (November 26): 811–823. doi:10.1016/j.immuni.2007.09.011. http://dx.doi.org/10.1016/j.immuni.2007.09.011.1074-76131097-4180http://nrs.harvard.edu/urn-3:HUL.InstRepos:13348330The 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.en-USJournal Article10.1016/j.immuni.2007.09.011