The mechanism and function of mitogen-activated protein kinase activation by ARF1

Fuguo Zhou, Chunmin Dong, Jason E. Davis, William H. Wu, Kristen Surrao, Guangyu Wu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Mitogen-activated protein kinases (MAPK) can be activated by a number of biochemical pathways through distinct signaling molecules. We have recently revealed a novel function for the Ras-like small GTPase ADP-ribosylation factor 1 (ARF1) in mediating the activation of Raf1-MEK-ERK1/2 pathway by G protein-coupled receptors [Dong C, Li C and Wu G (2011) J Biol Chem 286, 43,361-43,369]. Here, we have further defined the underlying mechanism and the possible function of ARF1-mediated MAPK pathway. We demonstrated that the blockage of ARF1 activation and the disruption of ARF1 localization to the Golgi by mutating Thr48, a highly conserved residue involved in the exchange of GDP for GTP, and the myristoylation site Gly2 abolished ARF1's ability to activate ERK1/2. In addition, treatment with Golgi structure disrupting agents markedly attenuated ARF1-mediated ERK1/2 activation. Furthermore, ARF1 significantly promoted cell proliferation. More interestingly, ARF1 activated 90. kDa ribosomal S6 kinase 1 (RSK1) without influencing Elk-1 activation and ERK2 translocation to the nuclei. These data demonstrate that, once activated, ARF1 activates the MAPK pathway likely using the Golgi as a main platform, which in turn activates the cytoplasmic RSK1, leading to cell proliferation.

Original languageEnglish (US)
Pages (from-to)2035-2044
Number of pages10
JournalCellular Signalling
Volume27
Issue number10
DOIs
StatePublished - Oct 1 2015

Fingerprint

ADP-Ribosylation Factor 1
Mitogen-Activated Protein Kinases
Ribosomal Protein S6 Kinases
Cell Proliferation
Monomeric GTP-Binding Proteins
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase Kinases
G-Protein-Coupled Receptors
Guanosine Triphosphate

Keywords

  • ARF1
  • Cell proliferation
  • ERK1/2
  • G protein
  • G protein-coupled receptor
  • MAPK
  • RSK1

ASJC Scopus subject areas

  • Cell Biology

Cite this

The mechanism and function of mitogen-activated protein kinase activation by ARF1. / Zhou, Fuguo; Dong, Chunmin; Davis, Jason E.; Wu, William H.; Surrao, Kristen; Wu, Guangyu.

In: Cellular Signalling, Vol. 27, No. 10, 01.10.2015, p. 2035-2044.

Research output: Contribution to journalArticle

Zhou, Fuguo ; Dong, Chunmin ; Davis, Jason E. ; Wu, William H. ; Surrao, Kristen ; Wu, Guangyu. / The mechanism and function of mitogen-activated protein kinase activation by ARF1. In: Cellular Signalling. 2015 ; Vol. 27, No. 10. pp. 2035-2044.
@article{823b19eff0d54de59e5d36efae2b27ed,
title = "The mechanism and function of mitogen-activated protein kinase activation by ARF1",
abstract = "Mitogen-activated protein kinases (MAPK) can be activated by a number of biochemical pathways through distinct signaling molecules. We have recently revealed a novel function for the Ras-like small GTPase ADP-ribosylation factor 1 (ARF1) in mediating the activation of Raf1-MEK-ERK1/2 pathway by G protein-coupled receptors [Dong C, Li C and Wu G (2011) J Biol Chem 286, 43,361-43,369]. Here, we have further defined the underlying mechanism and the possible function of ARF1-mediated MAPK pathway. We demonstrated that the blockage of ARF1 activation and the disruption of ARF1 localization to the Golgi by mutating Thr48, a highly conserved residue involved in the exchange of GDP for GTP, and the myristoylation site Gly2 abolished ARF1's ability to activate ERK1/2. In addition, treatment with Golgi structure disrupting agents markedly attenuated ARF1-mediated ERK1/2 activation. Furthermore, ARF1 significantly promoted cell proliferation. More interestingly, ARF1 activated 90. kDa ribosomal S6 kinase 1 (RSK1) without influencing Elk-1 activation and ERK2 translocation to the nuclei. These data demonstrate that, once activated, ARF1 activates the MAPK pathway likely using the Golgi as a main platform, which in turn activates the cytoplasmic RSK1, leading to cell proliferation.",
keywords = "ARF1, Cell proliferation, ERK1/2, G protein, G protein-coupled receptor, MAPK, RSK1",
author = "Fuguo Zhou and Chunmin Dong and Davis, {Jason E.} and Wu, {William H.} and Kristen Surrao and Guangyu Wu",
year = "2015",
month = "10",
day = "1",
doi = "10.1016/j.cellsig.2015.06.007",
language = "English (US)",
volume = "27",
pages = "2035--2044",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier Inc.",
number = "10",

}

TY - JOUR

T1 - The mechanism and function of mitogen-activated protein kinase activation by ARF1

AU - Zhou, Fuguo

AU - Dong, Chunmin

AU - Davis, Jason E.

AU - Wu, William H.

AU - Surrao, Kristen

AU - Wu, Guangyu

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Mitogen-activated protein kinases (MAPK) can be activated by a number of biochemical pathways through distinct signaling molecules. We have recently revealed a novel function for the Ras-like small GTPase ADP-ribosylation factor 1 (ARF1) in mediating the activation of Raf1-MEK-ERK1/2 pathway by G protein-coupled receptors [Dong C, Li C and Wu G (2011) J Biol Chem 286, 43,361-43,369]. Here, we have further defined the underlying mechanism and the possible function of ARF1-mediated MAPK pathway. We demonstrated that the blockage of ARF1 activation and the disruption of ARF1 localization to the Golgi by mutating Thr48, a highly conserved residue involved in the exchange of GDP for GTP, and the myristoylation site Gly2 abolished ARF1's ability to activate ERK1/2. In addition, treatment with Golgi structure disrupting agents markedly attenuated ARF1-mediated ERK1/2 activation. Furthermore, ARF1 significantly promoted cell proliferation. More interestingly, ARF1 activated 90. kDa ribosomal S6 kinase 1 (RSK1) without influencing Elk-1 activation and ERK2 translocation to the nuclei. These data demonstrate that, once activated, ARF1 activates the MAPK pathway likely using the Golgi as a main platform, which in turn activates the cytoplasmic RSK1, leading to cell proliferation.

AB - Mitogen-activated protein kinases (MAPK) can be activated by a number of biochemical pathways through distinct signaling molecules. We have recently revealed a novel function for the Ras-like small GTPase ADP-ribosylation factor 1 (ARF1) in mediating the activation of Raf1-MEK-ERK1/2 pathway by G protein-coupled receptors [Dong C, Li C and Wu G (2011) J Biol Chem 286, 43,361-43,369]. Here, we have further defined the underlying mechanism and the possible function of ARF1-mediated MAPK pathway. We demonstrated that the blockage of ARF1 activation and the disruption of ARF1 localization to the Golgi by mutating Thr48, a highly conserved residue involved in the exchange of GDP for GTP, and the myristoylation site Gly2 abolished ARF1's ability to activate ERK1/2. In addition, treatment with Golgi structure disrupting agents markedly attenuated ARF1-mediated ERK1/2 activation. Furthermore, ARF1 significantly promoted cell proliferation. More interestingly, ARF1 activated 90. kDa ribosomal S6 kinase 1 (RSK1) without influencing Elk-1 activation and ERK2 translocation to the nuclei. These data demonstrate that, once activated, ARF1 activates the MAPK pathway likely using the Golgi as a main platform, which in turn activates the cytoplasmic RSK1, leading to cell proliferation.

KW - ARF1

KW - Cell proliferation

KW - ERK1/2

KW - G protein

KW - G protein-coupled receptor

KW - MAPK

KW - RSK1

UR - http://www.scopus.com/inward/record.url?scp=84938092428&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938092428&partnerID=8YFLogxK

U2 - 10.1016/j.cellsig.2015.06.007

DO - 10.1016/j.cellsig.2015.06.007

M3 - Article

C2 - 26169956

AN - SCOPUS:84938092428

VL - 27

SP - 2035

EP - 2044

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 10

ER -