title: Grb2 interacts with SGEF and antagonizes the ability of SGEF to enhance EGF-induced ERK1/2 activation.
abstract: Previously, we demonstrated that SGEF enhances EGFR stability; however, SGEF-mediated downstream signaling of EGFR is not well understood. Here, we show that SGEF enhances EGF-induced ERK1/2 activation independent of its guanine nucleotide exchange (GEF) activity. We further show that SGEF interacts with Grb2, a critical downstream transducer of EGFR. Surprisingly, we found that interaction of Grb2 to SGEF antagonizes the ability of SGEF to enhance EGF-induced ERK1/2 activation. Taken together, this study reports a novel function of SGEF that excludes GEF and also provides important insights into the complex role of Grb2 in EGFR signal transduction.
authors.affiliation: Laboratory of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Taiping Road, Haidian, Beijing, 100850, People's Republic of China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wang
authors.forename: Shanhu
authors.initials: S
authors.lastname: Li
authors.forename: Hailiang
authors.initials: H
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.forename: Guolan
authors.initials: G
authors.lastname: Luo
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Jianguang
authors.initials: J
authors.lastname: Zhou
mesh_terms: D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C473930:ARHGEF26 protein, human; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D020662:Guanine Nucleotide Exchange Factors; D004815:Epidermal Growth Factor