MEKK1 phosphorylates MEK1 and MEK2 but does not cause activation of mitogen-activated protein kinase

Shuichan Xu, David Robbins, Jeff Frost, Alphonsus Dang, Carol Lange-Carter, Melanie H. Cobb

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A constitutively active fragment of rat MEK kinase 1 (MEKK1) consisting of only its catalytic domain (MEKK-C) expressed in bacteria quantitatively activates recombinant mitogen-activated protein (MAP) kinase/extracellular signal-regulated protein kinase (ERK) kinases 1 and 2 (MEK1 and MEK2) in vitro. Activation of MEK1 by MEKK-C is accompanied by phosphorylation of S218 and S222, which are also phosphorylated by the protein kinases c-Mos and Raf- 1. MEKK1 has been implicated in regulation of a parallel but distinct cascade that leads to phosphorylation of N-terminal sites on c-Jun; thus, its role in the MAP kinase pathway has been questioned. However, in addition to its capacity to phosphorylate MEK1 in vitro, MEKK-C interacts with MEK1 in the two-hybrid system, and expression of mouse MEKK1 or MEKK-C in mammalian cells causes constitutive activation of both MEK1 and MEK2. Neither cotransfected nor endogenous ERK2 is highly activated by MEKK1 compared to its stimulation by epidermal growth factor in spite of significant activation of endogenous MEK. Thus, other as yet undefined mechanisms may be involved in determining information flow through the MAP kinase and related pathways.

Original languageEnglish (US)
Pages (from-to)6808-6812
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number15
StatePublished - Jul 18 1995
Externally publishedYes


  • Jun N-terminal kinase
  • extracellular signal-related protein kinase
  • protein kinase cascades
  • stress-activated protein kinase


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