Raf-1 activates MAP kinase-kinase

@article{Kyriakis1992Raf1AM,
  title={Raf-1 activates MAP kinase-kinase},
  author={John M. Kyriakis and Harald App and Xian-feng Zhang and Papia Banerjee and David L. Brautigan and Ulf R{\"u}diger Rapp and Joseph Avruch},
  journal={Nature},
  year={1992},
  volume={358},
  pages={417-421}
}
THE normal cellular homologue of the acutely transforming oncogene v-ra/is c-raf-l, which encodes a serine/threonine protein kinase that is activated by many extracellular stimuli1. The physiological substrates of the protein c-Raf-1 are unknown. The mitogen-activated protein (MAP) kinases ErkI and 2 are also activated by mitogens through phosphorylation of Erk tyrosine and threonine residues catalysed by a protein kinase of relative molecular mass 50,000, MAP kinase-kinase (MAPK-K)2–7. Here we… 
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Raf1: Raf1 protein kinase (vertebrates)
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TLDR
The observation that Raf-1 and PKCα cooperate in the transformation of NIH3T3 cells is consistent with such a direct interaction, and the Ser499 phosphorylation site is necessary for this synergism.
Reconstitution of the Raf-1—MEK—ERK Signal Transduction Pathway In Vitro
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It is concluded that MEK is a direct substrate of Raf-1 and that the activation of MEK by Raf- 1 is due to phosphorylation by Raf -1, which is sufficient for MEK activation.
Mechanism of inhibition of Raf-1 by protein kinase A
TLDR
Using purified proteins, it is shown that in addition to weakening the interaction of Raf-1 with Ras, PKA can inhibit Raf- 1 function directly via phosphorylation of the Raf-2 kinase domain.
Signal transduction pathways involving the raf proto-oncogene
TLDR
Accumulating evidence indicates that membrane tyrosine kinases, ras, Raf-1, MEK and MAP kinase are interconnected via a complex network rather than via a linear pathway involving multiple substrates and feedback loops.
From RAS to MAPK: Cell-Free Assay System for RAS- and Rap1–Dependent B-Raf Activation
It is well established that RAS activates the MAP kinase cascade, consisting of the mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase (ERK), ERK kinase (MEK) and MEK kinase…
Critical tyrosine residues regulate the enzymatic and biological activity of Raf-1 kinase
TLDR
It is demonstrated that maturation of the tyrosine phosphorylation sites can dramatically alter the function of Raf-1 and this is the first report that a transforming Raf- 1 protein can be generated by a single amino acid substitution.
Growth Factors Induce Nuclear Translocation of MAP
TLDR
It is proposed that the rapid and persistent nuclear transfer of p42 "~k and IM4 " ~ during the entire G0-G1 period is crucial for the function of these kinases in mediating the growth.
Selective Activation of MEK1 but Not MEK2 by A-Raf from Epidermal Growth Factor-stimulated Hela Cells (*)
TLDR
It is demonstrated that A-Raf is, indeed, a MEK1 activator and may play a role in growth factor signaling, and observations seem to suggest a general strategy using mutants to identify the upstream kinase of a phosphoprotein or the downstream targets of a kinase.
MEKK1 Binds Raf-1 and the ERK2 Cascade Components*
TLDR
It is demonstrated that endogenous MEKK1 binds to endogenous ERK2, MEK1, and another MEKK level kinase, Raf-1, suggesting that it can assemble all three proteins of the ERK1/2 MAP kinase module.
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References

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TLDR
Evidence is presented that mitogen-activated protein-serine (MAP) kinases (pp54 and pp42/44) specifically phosphorylate these sites and that their phosphorylation positively regulates the transacting activity of c-jun.
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TLDR
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TLDR
It is demonstrated that MAP kinase is only active when both tyrosyl and threonyl residues are phosphorylated and suggested therefore that the enzyme functions in vivo to integrate signals from two distinct transduction pathways.
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TLDR
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TLDR
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TLDR
The serine/threonine kinase Raf-1 may be a substrate for MAP kinase in vivo, and this peptide also undergoes an insulin-dependent increase in labelling.
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TLDR
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