title: Trihydrophobin 1 phosphorylation by c-Src regulates MAPK/ERK signaling and cell migration.
abstract: c-Src activates Ras-MAPK/ERK signaling pathway and regulates cell migration, while trihydrophobin 1 (TH1) inhibits MAPK/ERK activation and cell migration through interaction with A-Raf and PAK1 and inhibiting their kinase activities. Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1. Further study reveals that Tyr-6 phosphorylation of TH1 reduces its inhibition on MAPK/ERK signaling, enhances c-Src mediated cell migration. Moreover, induced tyrosine phosphorylation of TH1 has been found by EGF and estrogen treatments. Taken together, our findings demonstrate a novel mechanism for the comprehensive regulation of Ras/Raf/MEK/ERK signaling and cell migration involving tyrosine phosphorylation of TH1 by c-Src.
authors.affiliation: Gene Research Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Wu
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Sun
authors.forename: Jingwen
authors.initials: J
authors.lastname: Wu
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Peng
authors.forename: Huacheng
authors.initials: H
authors.lastname: Gan
authors.forename: Chunyi
authors.initials: C
authors.lastname: Zhang
authors.forename: Lingling
authors.initials: L
authors.lastname: Ji
authors.forename: Jianhui
authors.initials: J
authors.lastname: Xie
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhu
authors.forename: Shifang
authors.initials: S
authors.lastname: Ren
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
authors.forename: Songwen
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019556:COS Cells; D000081247:CSK Tyrosine-Protein Kinase; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000235:genetics / Q000502:physiology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D010766:Phosphorylation / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases
chemical_list: D002352:Carrier Proteins; D014157:Transcription Factors; C118437:negative elongation factor; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human