Gene interactions and pathways from curated databases and text-mining
J Biol Chem 1993, PMID: 8226933

Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases.

Zheng, C F; Guan, K L

Activation of extracellular signal-regulated kinase (ERK) or mitogen-activated protein kinase by MEK (mitogen-activated protein kinase or extracellular signal-regulated kinase kinase) is an essential event in the mitogenic growth factor signal transduction. We now demonstrate that three recombinant MEKs (MEK1, MEK2, MEK3) show remarkably different activity toward recombinant ERK1 and ERK2. MEK2 is the most active ERK activator. The recombinant MEK1 has an activity approximately seven times lower than that of MEK2. MEK3, which is identical to MEK1 except for missing an internal 26-amino acid residue and probably represents an alternative splicing product of MEK1, shows neither autophosphorylation nor ERK-activating activity. Recombinant MEK1 and MEK2 can be activated by epidermal growth factor-stimulated SWISS3T3 cell lysate. MEK1 and MEK2 can also be activated by autophosphorylation. Autophosphorylation of MEKs correlates with their ability to phosphorylate and activate ERKs. Phosphorylation of MEK is also stimulated by ERK. Phosphoamino acid analysis showed that ERK1 preferentially phosphorylated threonine residue of MEKs. MEKs complex with ERKs in vitro. Interestingly, MEK3 also forms a complex with ERK1, although it is totally inactive as an ERK activator.

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Text Mining Data

ERK → MEK2: " MEK2 is the most active ERK activator "

Manually curated Databases

  • IRef Biogrid Interaction: MAPK3 — MAP2K3 (direct interaction, pull down)
  • IRef Biogrid Interaction: MAPK3 — MAP2K1 (direct interaction, pull down)
  • IRef Biogrid Interaction: MAPK3 — MAP2K1 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: MAP2K2 — MAPK3 (direct interaction, pull down)
  • IRef Biogrid Interaction: MAP2K2 — MAPK3 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: MAP2K1 — MAP2K1 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: MAP2K2 — MAP2K2 (direct interaction, enzymatic study)
  • IRef Hprd Interaction: MAPK3 — MAP2K3 (in vitro)
  • IRef Hprd Interaction: MAPK3 — MAP2K1 (in vivo)
  • IRef Hprd Interaction: MAPK3 — MAP2K1 (in vitro)
  • IRef Hprd Interaction: MAP2K2 — MAPK3 (in vitro)
  • IRef Hprd Interaction: MAP2K1 — MAP2K1 (in vitro)
  • IRef Hprd Interaction: MAP2K1 — MAP2K1 (in vivo)
  • IRef Hprd Interaction: MAP2K2 — MAP2K2 (in vitro)
  • IRef Innatedb Interaction: MAP2K3 — MAPK3 (unknown, -)
  • NCI Pathway Database ErbB1 downstream signaling: Erk1-2 (MAPK3/MAPK1) → Erk1-2-active (MAPK3/MAPK1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database ErbB1 downstream signaling: Erk1-2 (MAPK3/MAPK1) → MEK1 (MAP2K1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database ErbB1 downstream signaling: Erk1-2 (MAPK3/MAPK1) → IQGAP1 (IQGAP1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database ErbB1 downstream signaling: MEK1 (MAP2K1) → IQGAP1 (IQGAP1) (modification, activates)
    Evidence: assay, physical interaction
  • NCI Pathway Database ErbB1 downstream signaling: Erk1-2 (MAPK3/MAPK1) → Erk1-2-active (MAPK3/MAPK1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database ErbB1 downstream signaling: Erk1-2 (MAPK3/MAPK1) → MEK1 (MAP2K1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database ErbB1 downstream signaling: Erk1-2 (MAPK3/MAPK1) → KSR (KSR1) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database ErbB1 downstream signaling: MEK1 (MAP2K1) → KSR (KSR1) (modification, activates)
    Evidence: assay, physical interaction
In total, 15 gene pairs are associated to this article in curated databases