Synergistic activation by Ras and 14-3-3 protein of a mitogen-activated protein kinase kinase kinase named Ras-dependent extracellular signal-regulated kinase kinase stimulator

K Shimizu; S Kuroda; B Yamamori; S Matsuda; K Kaibuchi; T Yamauchi; T Isobe; K Irie; K Matsumoto; Y Takai

Synergistic activation by Ras and 14-3-3 protein of a mitogen-activated protein kinase kinase kinase named Ras-dependent extracellular signal-regulated kinase kinase stimulator

J Biol Chem. 1994 Sep 16;269(37):22917-20.

Authors

K Shimizu¹, S Kuroda, B Yamamori, S Matsuda, K Kaibuchi, T Yamauchi, T Isobe, K Irie, K Matsumoto, Y Takai

Affiliation

¹ Department of Molecular Biology and Biochemistry, Osaka University Medical School, Japan.

PMID: 8083186

Abstract

We have identified, in Xenopus oocyte cytosol, a protein kinase named REKS (Ras-dependent extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase kinase (MEK) stimulator), which phosphorylates and activates recombinant ERK2 through recombinant MEK in a recombinant GTP gamma S (guanosine 5'-(3-O-thio)triphosphate)-Ras-dependent manner. We show here that this REKS activity is synergistically enhanced by a combination of mammalian recombinant GTP gamma S-KiRas and 14-3-3 protein purified from rat brain. 14-3-3 protein is known to activate tyrosine and tryptophan hydroxylases, to modulate the protein kinase C activity, to stimulate secretion, and to show phospholipase A2 activity per se. 14-3-3 protein did not affect the MEK activity. 14-3-3 protein neither interacted with Ki-Ras nor affected the neurofibromin activity to stimulate the GTPase activity of Ki-Ras under the conditions where the recombinant N-terminal fragment of c-Raf-1 inhibited it. These results suggest that 14-3-3 protein has an additional function in the regulation of the Ras-MEK-ERK cascade pathway through the activation of REKS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

14-3-3 Proteins
Amino Acid Sequence
Animals
Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases*
Female
Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
MAP Kinase Kinase Kinases*
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
Molecular Sequence Data
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Oncogene Protein p21(ras) / metabolism*
Oocytes
Phosphorylation
Protein Kinases / metabolism
Protein Serine-Threonine Kinases / metabolism
Protein-Tyrosine Kinases / metabolism
Rats
Tyrosine 3-Monooxygenase*
Xenopus Proteins
Xenopus laevis

Substances

14-3-3 Proteins
Nerve Tissue Proteins
Xenopus Proteins
Guanosine 5'-O-(3-Thiotriphosphate)
Tyrosine 3-Monooxygenase
Protein Kinases
Protein-Tyrosine Kinases
Protein Serine-Threonine Kinases
Calcium-Calmodulin-Dependent Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase 1
MAP Kinase Kinase Kinases
REKS protein, Xenopus
Ras-dependent mitogen-activated protein kinase kinase kinase
Mitogen-Activated Protein Kinase Kinases
Oncogene Protein p21(ras)