Hyun Sub Hwang | Yonsei University (original) (raw)
Supervisors: Eui-Ju Choi and Dong-Wook Kim
less
Uploads
Papers by Hyun Sub Hwang
BSTRACT Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotideexchange factor (GEF) that ... more BSTRACT Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotideexchange factor (GEF) that mediates intracellular signaling processes induced by receptor tyrosine kinases. In this study, we show that CIIA (also known as VPS28) physically associates with SOS1 and thereby inhibits the GEF activity of SOS1 on Ras, which prevents the epidermal growth factor (EGF)-induced activation of the Ras-Erk1/2 pathway. Furthermore, CIIA inhibited cyclin D1 expression, as well as DNA, synthesis in response to EGF. Intriguingly, CIIA failed to inhibit the Ras-specific GEF activity of Noonan-syndrome-associated SOS1 mutants (M269R, R552G, W729L and E846K). Taken together, our results suggest that CIIA functions as a negative modulator of the SOS1-Ras signaling events initiated by peptide growth factors including EGF.
The Journal of Cell …, Jan 1, 2011
Correspondence to Eui-Ju Choi: ejchoi@korea.ac.kr Abbreviations used in this paper: CRIB, Cdc42 a... more Correspondence to Eui-Ju Choi: ejchoi@korea.ac.kr Abbreviations used in this paper: CRIB, Cdc42 and Rac1 interactive binding; DH, diffuse B cell lymphoma homology; GEF, guanine nucleotide exchange factor; mant, N-methylanthraniloyl; PH, pleckstrin homology; RBD, Ras-GTP binding domain; REM, Ras exchanger motif; RTK, receptor tyrosine kinase; SOS1, son of sevenless 1.
BSTRACT Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotideexchange factor (GEF) that ... more BSTRACT Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotideexchange factor (GEF) that mediates intracellular signaling processes induced by receptor tyrosine kinases. In this study, we show that CIIA (also known as VPS28) physically associates with SOS1 and thereby inhibits the GEF activity of SOS1 on Ras, which prevents the epidermal growth factor (EGF)-induced activation of the Ras-Erk1/2 pathway. Furthermore, CIIA inhibited cyclin D1 expression, as well as DNA, synthesis in response to EGF. Intriguingly, CIIA failed to inhibit the Ras-specific GEF activity of Noonan-syndrome-associated SOS1 mutants (M269R, R552G, W729L and E846K). Taken together, our results suggest that CIIA functions as a negative modulator of the SOS1-Ras signaling events initiated by peptide growth factors including EGF.
The Journal of Cell …, Jan 1, 2011
Correspondence to Eui-Ju Choi: ejchoi@korea.ac.kr Abbreviations used in this paper: CRIB, Cdc42 a... more Correspondence to Eui-Ju Choi: ejchoi@korea.ac.kr Abbreviations used in this paper: CRIB, Cdc42 and Rac1 interactive binding; DH, diffuse B cell lymphoma homology; GEF, guanine nucleotide exchange factor; mant, N-methylanthraniloyl; PH, pleckstrin homology; RBD, Ras-GTP binding domain; REM, Ras exchanger motif; RTK, receptor tyrosine kinase; SOS1, son of sevenless 1.