Gene interactions and pathways from curated databases and text-mining
Oncogene 1995, PMID: 7731720

B-Raf protein isoforms interact with and phosphorylate Mek-1 on serine residues 218 and 222.

Papin, C; Eychène, A; Brunet, A; Pagès, G; Pouysségur, J; Calothy, G; Barnier, J V

The B-raf/c-Rmil proto-oncogene belongs to the raf/mil family of serine/threonine protein kinases. It encodes multiple protein isoforms resulting from alternative splicing of two exons located upstream of the kinase domain. Recent studies suggested that B-Raf could be the intermediate molecule between Ras and Mek-1 (MAP Kinase Kinase) in signalling pathways specific of neural cells. However, there has been no evidence for a direct interaction between B-Raf and Mek-1. We report here that different B-Raf isoforms can be co-immunoprecipitated with anti-Mek-1 antisera in COS-1 cells and that the kinase activity of B-Raf is not required for its interaction with Mek-1. We also show that all B-Raf isoforms tested phosphorylate Mek-1 in a time-dependent manner, whereas kinase defective mutants fail to do so. Finally, we demonstrate that the constitutively activated S218D, S222D and S218D/S222D mutants of Mek-1 interact similarly with B-Raf. However, only the S218D and S222D mutants, and not the S218D/S222D double mutant, can be phosphorylated by B-Raf isoforms. Therefore, serine residues 218 and 222, previously shown to regulate Mek-1 activity, appear to be the major phosphorylation sites by B-Raf in vitro.

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Text Mining Data

Mek-1 → B-Raf: " We report here that different B-Raf isoforms can be co-immunoprecipitated with anti-Mek-1 antisera in COS-1 cells and that the kinase activity of B-Raf is not required for its interaction with Mek-1 "

Manually curated Databases

  • IRef Hprd Interaction: MAP2K1 — BRAF (in vivo)
  • IRef Hprd Interaction: MAP2K1 — BRAF (in vitro)
  • IRef Hprd Interaction: ARAF — MAP2K1 (in vitro)
  • IRef Hprd Interaction: RAF1 — MAP2K1 (in vivo)
  • IRef Hprd Interaction: RAF1 — MAP2K1 (in vitro)
  • IRef Ophid Interaction: MAP2K1 — BRAF (aggregation, confirmational text mining)
  • NCI Pathway Database PDGFR-beta signaling pathway: KSR/14-3-3 (dimer)/MEK1-2-active complex (KSR1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB-MAP2K1_MAP2K2) → KSR/14-3-3 /MEK1-2 complex (KSR1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB-MAP2K1_MAP2K2) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database PDGFR-beta signaling pathway: KSR/14-3-3 /MEK1-2 complex (KSR1-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB-MAP2K1_MAP2K2) → BRAF/14-3-3 complex (BRAF-YWHAH_YWHAZ_YWHAQ_SFN_YWHAE_YWHAG_YWHAB) (modification, collaborate)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database PDGFR-beta signaling pathway: MEK1-2-active (MAP2K1/MAP2K2) → MEK1-2 (MAP2K1/MAP2K2) (modification, collaborate)
    Evidence: assay
  • NCI Pathway Database PDGFR-beta signaling pathway: MEK1-2 (MAP2K1/MAP2K2) → BRAF (BRAF) (modification, collaborate)
    Evidence: assay
  • NCI Pathway Database ErbB1 downstream signaling: IQGAP1 (IQGAP1) → MEK1 (MAP2K1) (modification, activates)
    Evidence: assay, physical interaction
  • NCI Pathway Database ErbB1 downstream signaling: IQGAP1 (IQGAP1) → BRAF (BRAF) (modification, activates)
    Evidence: assay, physical interaction
  • WikiPathways Serotonin Receptor 4/6/7 and NR3C Signaling: BRAF → MAP2K1 (mim-necessary-stimulation)
In total, 69 gene pairs are associated to this article in curated databases