CIIA negatively regulates the Ras-Erk1/2 signaling pathway through inhibiting the Ras-specific GEF activity of SOS1

Hyun Sub Hwang, Sang Gil Hwang, Kyoung Wan Yoon, Je Hyun Yoon, Kyung Hye Roh, Eui Ju Choi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotide-exchange 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.

Original languageEnglish
Pages (from-to)1640-1646
Number of pages7
JournalJournal of Cell Science
Volume127
Issue number8
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

ras Guanine Nucleotide Exchange Factors
Epidermal Growth Factor
Noonan Syndrome
Guanine Nucleotide Exchange Factors
Cyclin D1
Receptor Protein-Tyrosine Kinases
Intercellular Signaling Peptides and Proteins
Peptides
DNA

Keywords

  • CIIA
  • Ras
  • SOS1
  • VPS28

ASJC Scopus subject areas

  • Cell Biology

Cite this

CIIA negatively regulates the Ras-Erk1/2 signaling pathway through inhibiting the Ras-specific GEF activity of SOS1. / Hwang, Hyun Sub; Hwang, Sang Gil; Yoon, Kyoung Wan; Yoon, Je Hyun; Roh, Kyung Hye; Choi, Eui Ju.

In: Journal of Cell Science, Vol. 127, No. 8, 01.01.2014, p. 1640-1646.

Research output: Contribution to journalArticle

Hwang, Hyun Sub ; Hwang, Sang Gil ; Yoon, Kyoung Wan ; Yoon, Je Hyun ; Roh, Kyung Hye ; Choi, Eui Ju. / CIIA negatively regulates the Ras-Erk1/2 signaling pathway through inhibiting the Ras-specific GEF activity of SOS1. In: Journal of Cell Science. 2014 ; Vol. 127, No. 8. pp. 1640-1646.
@article{b6fb40829be5445b89c57f8ca3a2d764,
title = "CIIA negatively regulates the Ras-Erk1/2 signaling pathway through inhibiting the Ras-specific GEF activity of SOS1",
abstract = "Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotide-exchange 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.",
keywords = "CIIA, Ras, SOS1, VPS28",
author = "Hwang, {Hyun Sub} and Hwang, {Sang Gil} and Yoon, {Kyoung Wan} and Yoon, {Je Hyun} and Roh, {Kyung Hye} and Choi, {Eui Ju}",
year = "2014",
month = "1",
day = "1",
doi = "10.1242/jcs.139931",
language = "English",
volume = "127",
pages = "1640--1646",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "8",

}

TY - JOUR

T1 - CIIA negatively regulates the Ras-Erk1/2 signaling pathway through inhibiting the Ras-specific GEF activity of SOS1

AU - Hwang, Hyun Sub

AU - Hwang, Sang Gil

AU - Yoon, Kyoung Wan

AU - Yoon, Je Hyun

AU - Roh, Kyung Hye

AU - Choi, Eui Ju

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotide-exchange 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.

AB - Son of sevenless 1 (SOS1) is a Ras-specific guanine-nucleotide-exchange 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.

KW - CIIA

KW - Ras

KW - SOS1

KW - VPS28

UR - http://www.scopus.com/inward/record.url?scp=84898836513&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84898836513&partnerID=8YFLogxK

U2 - 10.1242/jcs.139931

DO - 10.1242/jcs.139931

M3 - Article

C2 - 24522193

AN - SCOPUS:84898836513

VL - 127

SP - 1640

EP - 1646

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 8

ER -