Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein

Jung Yeon Lim, Hongtae Kim, Sin Soo Jeun, Seok-Gu Kang, Kyung Jin Lee

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Numerous studies have suggested that the NF2 protein merlin is involved in the regulation of abnormal cell growth and proliferation. In this study, to better understand the merlin's mechanisms that contribute to the inhibition of tumorigenesis, we examined the potential action of merlin on the cell proliferative signaling pathways in response to growth hormone (GH). Merlin effectively attenuated the GH-induced serum response element (SRE) and Elk-1-mediated transcriptional activation, as well as the endogenous SRE-regulated gene c-fos expression in NIH3T3 cells. In addition, merlin prevented the Raf-1 complex activation process, which resulted in the suppression of MAP kinase/ERK, extracellular signal-regulated kinase (ERKs), and Elk-1 phosphorylation, which are the downstream signals of Raf-1. Moreover, it was shown that merlin interacted with endogenous growth factor receptor bound 2 (Grb2) protein and inhibited its expression. These results suggest that merlin contributes, via its protein-to-protein interaction with Grb2 and consequent inhibition of the MAPK pathways, to the regulation of the abnormal cell proliferation, and this provides a further mechanism underlying the tumor suppressor function of merlin.

Original languageEnglish
Pages (from-to)1151-1157
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume340
Issue number4
DOIs
Publication statusPublished - 2006 Feb 24

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GRB2 Adaptor Protein
Neurofibromin 2
MAP Kinase Signaling System
Growth Hormone
Serum Response Element
Cell proliferation
Chemical activation
Cell Proliferation
Cell signaling
fos Genes
Phosphorylation
Proteins
Growth Factor Receptors
Extracellular Signal-Regulated MAP Kinases
Cell growth
Transcriptional Activation
Action Potentials
Tumors
Carcinogenesis
Phosphotransferases

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lim, Jung Yeon ; Kim, Hongtae ; Jeun, Sin Soo ; Kang, Seok-Gu ; Lee, Kyung Jin. / Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 340, No. 4. pp. 1151-1157.
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Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein. / Lim, Jung Yeon; Kim, Hongtae; Jeun, Sin Soo; Kang, Seok-Gu; Lee, Kyung Jin.

In: Biochemical and Biophysical Research Communications, Vol. 340, No. 4, 24.02.2006, p. 1151-1157.

Research output: Contribution to journalArticle

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AU - Lee, Kyung Jin

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