Oncogene 1995,
PMID: 7731720
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