| First Author | Chang YJ | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 6 | Pages | 1003-19 |
| PubMed ID | 24396070 | Mgi Jnum | J:222134 |
| Mgi Id | MGI:5644006 | Doi | 10.1128/MCB.00940-13 |
| Citation | Chang YJ, et al. (2014) SH2B1beta interacts with STAT3 and enhances fibroblast growth factor 1-induced gene expression during neuronal differentiation. Mol Cell Biol 34(6):1003-19 |
| abstractText | Neurite outgrowth is an essential process during neuronal differentiation as well as neuroregeneration. Thus, understanding the molecular and cellular control of neurite outgrowth will benefit patients with neurological diseases. We have previously shown that overexpression of the signaling adaptor protein SH2B1beta promotes fibroblast growth factor 1 (FGF1)-induced neurite outgrowth (W. F. Lin, C. J. Chen, Y. J. Chang, S. L. Chen, I. M. Chiu, and L. Chen, Cell. Signal. 21:1060-1072, 2009). SH2B1beta also undergoes nucleocytoplasmic shuttling and regulates a subset of neurotrophin-induced genes. Although these findings suggest that SH2B1beta regulates gene expression, the nuclear role of SH2B1beta was not known. In this study, we show that SH2B1beta interacts with the transcription factor, signal transducer, and activator of transcription 3 (STAT3) in neuronal PC12 cells, cortical neurons, and COS7 fibroblasts. By affecting the subcellular distribution of STAT3, SH2B1beta increased serine phosphorylation and the concomitant transcriptional activity of STAT3. As a result, overexpressing SH2B1beta enhanced FGF1-induced expression of STAT3 target genes Egr1 and Cdh2. Chromatin immunoprecipitation assays further reveal that, in response to FGF1, overexpression of SH2B1beta promotes the in vivo occupancy of STAT3-Sp1 heterodimers at the promoter of Egr1 and Cdh2. These findings establish a central role of SH2B1beta in orchestrating signaling events to transcriptional activation through interacting and regulating STAT3-containing complexes during neuronal differentiation. |
