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Biochim Biophys Acta Mol Cell Res. 2018 Apr;1865(4):560-571. doi: 10.1016/j.bbamcr.2018.01.007. Epub 2018 Feb 4.

Ras-Raf-MAPK signaling promotes nuclear localization of FOXA transcription factor SGF1 via Ser91 phosphorylation.

Author information

1
Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology & School of Life Sciences, South China Normal University, Guangzhou 510631, China; Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China; Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
2
Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology & School of Life Sciences, South China Normal University, Guangzhou 510631, China.
3
Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China; School of Life Science, East China Normal University, Shanghai 200241, China.
4
School of Life Science, East China Normal University, Shanghai 200241, China.
5
Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Science and Technology & School of Life Sciences, South China Normal University, Guangzhou 510631, China; Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address: lisheng@scnu.edu.cn.

Abstract

Ras-Raf-MAPK signaling promotes cell proliferation and cell survival. We previously reported that Ras1CA overexpression, specifically in the posterior silk glands (PSGs) of the silkworm Bombyx mori, increased fibroin synthesis and cell size, resulting in improved silk yields. In this study, we compared the iTRAQ-based phosphoproteomic profiles of PSGs from wild-type and Ras1CA-overexpressing silkworms. Silk gland factor 1 (SGF1), a FOXA transcription factor that plays a critical role in activating fibroin gene expression, was identified as a phosphoprotein harboring Ser91 as a potential MAPK phosphorylation site. Ser91 phosphorylation of SGF1 was enhanced by Ras1CA overexpression, and this finding was verified by selected reaction monitoring. Consistently, MAPK activity is well correlated with Ser91 phosphorylation of SGF1 and its nuclear localization in PSG cells during silkworm development. Ras1CA overexpression and treatment with inhibitors of Ras signaling promoted or inhibited SGF1 nuclear localization, respectively; mutation of Ser91 to Ala91 eliminated SGF1 nuclear localization. Moreover, MAPK binds to SGF1 and directly phosphorylates Ser91, demonstrating Ser91 as a MAPK phosphorylation site in SGF1. In conclusion, Ras-Raf-MAPK signaling promotes SGF1 nuclear localization for transactivation via Ser91 phosphorylation in silkworms, showing that FOXA transcription factors are regulated via MAPK phosphorylation in animals.

KEYWORDS:

FOXA; Nuclear localization; Phosphorylation; Posterior silk gland; Ras-Raf-MAPK; Silk gland factor 1

PMID:
29355586
DOI:
10.1016/j.bbamcr.2018.01.007
[Indexed for MEDLINE]
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