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Participation of Gab1 and Gab2 in IL-22-mediated keratinocyte proliferation, migration, and differentiation

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Abstract

Interleukin-22 (IL-22) is one of the key mediators of keratinocyte alterations in psoriasis. IL-22 inhibits keratinocyte differentiation and induces the migration of human keratinocytes. Grb2-associated binder 1 (Gab1) has been shown to mediate epidermal growth factor-induced epidermal growth and differentiation via interaction with the Src homology-2-containing protein-tyrosine phosphatase (Shp2). In this investigation, we explore the role of Gab1 and Gab2 in IL-22-mediated keratinocyte activities. We show that both Gab1 and Gab2 were tyrosine phosphorylated in IL-22-stimulated HaCaT cells and human primary epidermal keratinocytes and contributed to the activation of Extracellular signal regulated kinase 1/2 (Erk1/2) through interaction with Shp2. We further demonstrate that HaCaT cells infected with adenoviruses expressing Shp2-binding-defective Gab1/2 mutants exhibited decreased cell proliferation and migration, as well as increased differentiation. Moreover, similar results were observed in HaCaT cells infected with adenovirus-based small interfering RNAs targeting Gab1 and/or Gab2. Altogether, these data underscore the critical roles of Gab1 and Gab2 in IL-22-mediated HaCaT cell proliferation, migration, and differentiation.

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Abbreviations

Erk:

Extracellular signal regulated kinase

MAPK:

Mitogen-activated protein kinase

Jnk:

C-Jun N-terminal kinase

DMEM:

Dulbecco’s modified Eagle’s medium

Gab:

Grb2-associated binder

Shp2:

Src homology-2 containing protein-tyrosine phosphatase

Stat:

Signal transducers and activators of transcription

EGF:

Epidermal growth factor

IL-22:

Interleukin-22

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Acknowledgments

This work was supported by National Natural Science Foundation of China (Grant No. 81173392).

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Authors and Affiliations

  1. Department of Dermatology of Clinical Medical School, Yangzhou University, Yangzhou, 225001, China

    Xiaofang Zhu

  2. College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, 225009, China

    Zhongliang Li, Wenyan Pan, Lu Qin, Guoqiang Zhu & Songshu Meng

  3. School of Medicine, Zhejiang University, Hangzhou, 310058, China

    Yuehai Ke

  4. Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    Jie Wu

  5. Department of Oncologic Sciences, University of South Florida, Tampa, FL, 33612, USA

    Jie Wu

  6. Medical College, Yangzhou University, Yangzhou, 225001, China

    Ping Bo

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  1. Xiaofang Zhu
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Correspondence to Ping Bo or Songshu Meng.

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Xiaofang Zhu, Zhongliang Li have contributed equally to this work.

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Zhu, X., Li, Z., Pan, W. et al. Participation of Gab1 and Gab2 in IL-22-mediated keratinocyte proliferation, migration, and differentiation. Mol Cell Biochem 369, 255–266 (2012). https://doi.org/10.1007/s11010-012-1389-5

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  • DOI: https://doi.org/10.1007/s11010-012-1389-5

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