Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members

Jeffrey A. Frost, Shuichan Xu, Michele R. Hutchison, Stevan Marcus, Melanie H. Cobb

Research output: Contribution to journalArticle

232 Citations (Scopus)

Abstract

The mitogen-activated protein (MAP) kinases are a family of serine/threonine kinases that are regulated by distinct extracellular stimuli. The currently known members include extracellular signal-regulated protein kinase 1 (ERK1), ERK2, the c-Jun N-terminal kinase/stress-activated protein kinases (JNK/SAPKs), and p38 MAP kinases. We find that overexpression of the Ste20-related enzymes p21-activated kinase 1 (PAK1) and PAK2 in 293 cells is sufficient to activate JNK/SAPK and to a lesser extent p38 MAP kinase but not ERK2. Rat MAP/ERK kinase kinase 1 can stimulate the activity of each of these MAP kinases. Although neither activated Rac nor the PAKs stimulate ERK2 activity, overexpression of either dominant negative Rac2 or the N-terminal regulatory domain of PAK1 inhibits Ras-mediated activation of ERK2, suggesting a permissive role for Rac in the control of the ERK pathway. Furthermore, constitutively active Rac2, Cdc42hs, and RhoA synergize with an activated form of Raf to increase ERK2 activity. These findings reveal a previously unrecognized connection between Rho family small G proteins and the ERK pathway.

Original languageEnglish (US)
Pages (from-to)3707-3713
Number of pages7
JournalMolecular and Cellular Biology
Volume16
Issue number7
StatePublished - 1996

Fingerprint

p21-Activated Kinases
Monomeric GTP-Binding Proteins
Mitogen-Activated Protein Kinases
Protein Kinases
MAP Kinase Signaling System
JNK Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
Heat-Shock Proteins
MAP Kinase Kinase 1
Mitogen-Activated Protein Kinase 3
Protein-Serine-Threonine Kinases
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members. / Frost, Jeffrey A.; Xu, Shuichan; Hutchison, Michele R.; Marcus, Stevan; Cobb, Melanie H.

In: Molecular and Cellular Biology, Vol. 16, No. 7, 1996, p. 3707-3713.

Research output: Contribution to journalArticle

Frost, Jeffrey A. ; Xu, Shuichan ; Hutchison, Michele R. ; Marcus, Stevan ; Cobb, Melanie H. / Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members. In: Molecular and Cellular Biology. 1996 ; Vol. 16, No. 7. pp. 3707-3713.
@article{85ec7d90af5f4dffa72d069dd4f0ed8b,
title = "Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members",
abstract = "The mitogen-activated protein (MAP) kinases are a family of serine/threonine kinases that are regulated by distinct extracellular stimuli. The currently known members include extracellular signal-regulated protein kinase 1 (ERK1), ERK2, the c-Jun N-terminal kinase/stress-activated protein kinases (JNK/SAPKs), and p38 MAP kinases. We find that overexpression of the Ste20-related enzymes p21-activated kinase 1 (PAK1) and PAK2 in 293 cells is sufficient to activate JNK/SAPK and to a lesser extent p38 MAP kinase but not ERK2. Rat MAP/ERK kinase kinase 1 can stimulate the activity of each of these MAP kinases. Although neither activated Rac nor the PAKs stimulate ERK2 activity, overexpression of either dominant negative Rac2 or the N-terminal regulatory domain of PAK1 inhibits Ras-mediated activation of ERK2, suggesting a permissive role for Rac in the control of the ERK pathway. Furthermore, constitutively active Rac2, Cdc42hs, and RhoA synergize with an activated form of Raf to increase ERK2 activity. These findings reveal a previously unrecognized connection between Rho family small G proteins and the ERK pathway.",
author = "Frost, {Jeffrey A.} and Shuichan Xu and Hutchison, {Michele R.} and Stevan Marcus and Cobb, {Melanie H.}",
year = "1996",
language = "English (US)",
volume = "16",
pages = "3707--3713",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members

AU - Frost, Jeffrey A.

AU - Xu, Shuichan

AU - Hutchison, Michele R.

AU - Marcus, Stevan

AU - Cobb, Melanie H.

PY - 1996

Y1 - 1996

N2 - The mitogen-activated protein (MAP) kinases are a family of serine/threonine kinases that are regulated by distinct extracellular stimuli. The currently known members include extracellular signal-regulated protein kinase 1 (ERK1), ERK2, the c-Jun N-terminal kinase/stress-activated protein kinases (JNK/SAPKs), and p38 MAP kinases. We find that overexpression of the Ste20-related enzymes p21-activated kinase 1 (PAK1) and PAK2 in 293 cells is sufficient to activate JNK/SAPK and to a lesser extent p38 MAP kinase but not ERK2. Rat MAP/ERK kinase kinase 1 can stimulate the activity of each of these MAP kinases. Although neither activated Rac nor the PAKs stimulate ERK2 activity, overexpression of either dominant negative Rac2 or the N-terminal regulatory domain of PAK1 inhibits Ras-mediated activation of ERK2, suggesting a permissive role for Rac in the control of the ERK pathway. Furthermore, constitutively active Rac2, Cdc42hs, and RhoA synergize with an activated form of Raf to increase ERK2 activity. These findings reveal a previously unrecognized connection between Rho family small G proteins and the ERK pathway.

AB - The mitogen-activated protein (MAP) kinases are a family of serine/threonine kinases that are regulated by distinct extracellular stimuli. The currently known members include extracellular signal-regulated protein kinase 1 (ERK1), ERK2, the c-Jun N-terminal kinase/stress-activated protein kinases (JNK/SAPKs), and p38 MAP kinases. We find that overexpression of the Ste20-related enzymes p21-activated kinase 1 (PAK1) and PAK2 in 293 cells is sufficient to activate JNK/SAPK and to a lesser extent p38 MAP kinase but not ERK2. Rat MAP/ERK kinase kinase 1 can stimulate the activity of each of these MAP kinases. Although neither activated Rac nor the PAKs stimulate ERK2 activity, overexpression of either dominant negative Rac2 or the N-terminal regulatory domain of PAK1 inhibits Ras-mediated activation of ERK2, suggesting a permissive role for Rac in the control of the ERK pathway. Furthermore, constitutively active Rac2, Cdc42hs, and RhoA synergize with an activated form of Raf to increase ERK2 activity. These findings reveal a previously unrecognized connection between Rho family small G proteins and the ERK pathway.

UR - http://www.scopus.com/inward/record.url?scp=0029950672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029950672&partnerID=8YFLogxK

M3 - Article

VL - 16

SP - 3707

EP - 3713

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 7

ER -