Direct interaction between Ras and the kinase domain of mitogen-activated protein kinase kinase kinase (MEKK1)

M. Russell, C. A. Lange-Carter, G. L. Johnson

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

Mitogen-activated protein kinase kinase kinase (MEKK1) is a serine- threonine kinase that regulates sequential protein kinase pathways involving stress-activated protein kinases and mitogen-activated protein kinases. MEKK1 is activated in response to growth factor stimulation of cells and by expression of activated Ras. We demonstrate that the kinase domain of MEKK1 (MEKK(COOH)) binds to GST-Ras(V12) in a GTP-dependent manner. Purified bacterially expressed MEKK(COOH) binds to GST-Ras(V12)(GTPγS) (GTPγS is guanosine 5'-3-O-(thio)triphosphate), demonstrating a direct interaction of the two proteins. A Ras effector domain peptide blocks the binding of MEKK(COOH) to GST-Ras(V12)(GTPγS). MEKK(COOH) complexed with GST- Ras(V12)(GTPγS) is capable of phosphorylating MEK1. These findings indicate that MEKK1 directly binds Ras·GTP. Thus, Ras interacts with protein kinases of both the Raf and MEKK families.

Original languageEnglish (US)
Pages (from-to)11757-11760
Number of pages4
JournalJournal of Biological Chemistry
Volume270
Issue number20
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

Dive into the research topics of 'Direct interaction between Ras and the kinase domain of mitogen-activated protein kinase kinase kinase (MEKK1)'. Together they form a unique fingerprint.

Cite this