title: SH2B1β interacts with STAT3 and enhances fibroblast growth factor 1-induced gene expression during neuronal differentiation.
abstract: 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 SH2B1β 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). SH2B1β also undergoes nucleocytoplasmic shuttling and regulates a subset of neurotrophin-induced genes. Although these findings suggest that SH2B1β regulates gene expression, the nuclear role of SH2B1β was not known. In this study, we show that SH2B1β 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, SH2B1β increased serine phosphorylation and the concomitant transcriptional activity of STAT3. As a result, overexpressing SH2B1β enhanced FGF1-induced expression of STAT3 target genes Egr1 and Cdh2. Chromatin immunoprecipitation assays further reveal that, in response to FGF1, overexpression of SH2B1β promotes the in vivo occupancy of STAT3-Sp1 heterodimers at the promoter of Egr1 and Cdh2. These findings establish a central role of SH2B1β in orchestrating signaling events to transcriptional activation through interacting and regulating STAT3-containing complexes during neuronal differentiation.
authors.affiliation: Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Chang
authors.forename: Kuan-Wei
authors.initials: KW
authors.lastname: Chen
authors.forename: Ching-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Ming-Hsing
authors.initials: MH
authors.lastname: Lin
authors.forename: Yuh-Ju
authors.initials: YJ
authors.lastname: Sun
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Lee
authors.forename: Ing-Ming
authors.initials: IM
authors.lastname: Chiu
authors.forename: Linyi
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D019556:COS Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D015820:Cadherins; D002352:Carrier Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D007136:Immunoglobulins; D047908:Intracellular Signaling Peptides and Proteins; C570099:N-cadherin, rat; D009419:Nerve Tissue Proteins; C492010:SH2B1 protein, rat; C090698:SP1 antigen; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D016220:Fibroblast Growth Factor 1