SH2B1β Interacts with STAT3 and Enhances Fibroblast Growth Factor 1-Induced Gene Expression during Neuronal Differentiation

Chang, Yu‐Jung; Chen, Kuan-Wei; Chen, Ching-Jen; Lin, Ming-Hsing; Sun, Yuh‐Ju; Lee, Jia-Lin; Chiu, Ing‐Ming; Chen, Linyi

doi:10.1128/mcb.00940-13

Cited by 17 publications

(14 citation statements)

References 89 publications

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“…In this study, we demonstrate that SH2B1 interacts with IRSp53 and promotes neurite outgrowth and neuronal branching. Based on the known interaction between SH2B1 and neurotrophin receptors at the cell surface during neuronal differentiation (18,19,(23)(24)(25), these results raise the possibility that SH2B1-IRSp53 complexes specify locations for filopodium formation through SH2B1-mediated signaling events. In line with this possibility, overexpression of SH2 domain only mutant, SH2B1␤(505-670), inhibits neurite outgrowth (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Human subjects with SH2B1 mutations display behavioral abnormalities, including social isolation and aggression (20 -22). Overexpressing SH2B1␤ has previously been shown to enhance neurite outgrowth of neuronal PC12 cells and cortical and hippocampal neurons (18,19,(23)(24)(25)(26). However, exactly how SH2B1 promotes neurite initiation remains unclear.…”

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confidence: 99%

“…SH2B1 contains two prolinerich domains, two actin-binding regions, a pleckstrin homology domain, and an SH2 domain. SH2B1 also has a nuclear localization sequence and a nuclear export sequence, which affect its cellular distribution and thus differentiation genes (15)(16)(17)(18)(19). Human subjects with SH2B1 mutations display behavioral abnormalities, including social isolation and aggression (20 -22).…”

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confidence: 99%

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SH2B1 and IRSp53 Proteins Promote the Formation of Dendrites and Dendritic Branches

Chen

Shih

Chang

et al. 2015

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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SH2B1 and IRSp53 Proteins Promote the Formation of Dendrites and Dendritic Branches

Chen

Shih

Chang

et al. 2015

Journal of Biological Chemistry

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“…At present, the connection between the SP1 signaling and ATL-1 has not been reported, thus, the potential role and function of SP1 in mediating the anti-cancer effects of ATL-1 remain to be determined. Moreover, the link of Stat3 and SP1 signaling in regulation of physio-pathological functions including growth, differentiation and progression have been observed in several studies [29-31] implying important roles of the interaction in signal transduction and tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Activation of ERK and Mutual Regulation of Stat3 and SP1 Contribute to Inhibition of PDK1 Expression by Atractylenolide-1 in Human Lung Cancer Cells

Xiao¹,

Zheng²,

Wu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Atractylodes macrocephula Koidz is an important ingredient in traditional Chinese herbs. One major bioactive compound, atractylenolide-1 (ATL-1), was reported to have anti-inflammatory and anti-tumor activities. However, the underlying molecular mechanism associated to this has not been well elucidated. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Western blot analysis was performed to examine the phosphorylation and protein expression of extracellular signaling-regulated kinase 1/2 (ERK1/2), signal transducer and activator of transcription 3 (Stat3), 3-phosphoinositide dependent protein kinase-1 (PDK1) and transcription factor SP1. QRT-PCR was used to examine the mRNA levels of PDK1 gene. Exogenously expressions of Stat3, PDK1 and SP1 were carried out by transient transfection assays. PDK1 promoter activity was measured by Secrete-Pair Dual Luminescence Assay Kit. A nude mice xenograft model was used to confirm the findings in vitro. Results: We showed that ATL-1 inhibited human lung cancer cell growth and induced cell cycle arrest. Furthermore, we found that ATL-1 stimulated phosphorylation of ERK1/2, inhibited phosphorylation and protein expressions of Stat3 and SP1; the latter were abrogated in the presence of MEK/ERK inhibitor PD98059. Moreover, ATL-1 reduced the protein, mRNA expression and promoter activity of PDK1. Intriguingly, exogenously expressed Stat3 and SP1 overcame ATL-1-inhibited SP1 and Stat3, and PDK1 protein expressions, respectively. Moreover, overexpression of PDK1 resisted the ATL-1-inhibited lung cancer cell growth. In consistent with the results in vitro, ATL-1 inhibited tumor growth, protein expressions of Stat3, SP1 and PDK1, and induced phosphorylation of ERK1/2 in vivo. Conclusion: In summary, our results show that ATL-1 inhibits lung cancer cell growth through activation of ERK1/2, followed by suppressing SP1 protein expression. ATL-1 also reduces phosphorylation and protein levels of Stat3. These are mutual regulation between Stat3 and SP1 proteins affected by ATL-1. This ultimately suppresses PDK1 gene expression. This study reveals a novel mechanism by which ATL-1 inhibits growth of lung cancer cells. Thus, targeting PDK1 pinpoints a potential in the lung cancer treatment.

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“…SH2B1 promotes neurite initiation, outgrowth and neuronal survival of PC12 cells, cortical and hippocampal neurons [31,35,37,38]. Besides general function as a signaling adaptor protein, SH2B1β also acts as a nuclear protein which shuttles between cytosol and nucleus to regulate expression of genes such as MMP3, MMP10, uPAR, Egr1 and Cdh2 [39][40][41]. In addition to promote cell differentiation and survival, SH2B1 is involved in actin-based motility [42].…”

Section: Introductionmentioning

confidence: 98%

SH2B1 increases the numbers of IRSp53-induced filopodia

Hong

Liu

Chen

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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SH2B1β Interacts with STAT3 and Enhances Fibroblast Growth Factor 1-Induced Gene Expression during Neuronal Differentiation

Cited by 17 publications

References 89 publications

SH2B1 and IRSp53 Proteins Promote the Formation of Dendrites and Dendritic Branches

SH2B1 and IRSp53 Proteins Promote the Formation of Dendrites and Dendritic Branches

Activation of ERK and Mutual Regulation of Stat3 and SP1 Contribute to Inhibition of PDK1 Expression by Atractylenolide-1 in Human Lung Cancer Cells

SH2B1 increases the numbers of IRSp53-induced filopodia

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