Raf-1 protein kinase is required for growth of induced NIH/3T3 cells

@article{Kolch1991Raf1PK,
  title={Raf-1 protein kinase is required for growth of induced NIH/3T3 cells},
  author={Walter Kolch and Gisela Heidecker and Patricia A. Lloyd and Ulf R{\"u}diger Rapp},
  journal={Nature},
  year={1991},
  volume={349},
  pages={426-428}
}
MANY growth factors regulate the cytoplasmic Raf-1 protein kinase1–10, consistent with its having a central role in transduction of growth signals. The kinase is ubiquitously expressed11 and can promote proliferation12, presumably in a manner dependent on growth-factor receptors and membrane-associated oncogenes13–15. We have now examined the dependence of serum- and TPA (12-O-tetradecanoylphorbol-13-acetate)-regulated NIH/3T3 cell growth on RAF-1 kinase to determine whether Raf-1 is essential… 
Induction of cell proliferation in quiescent NIH 3T3 cells by oncogenic c-Raf-1
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This finding indicates that oncogenic activation of the c-Raf-1 protein can trigger the entry into the cell cycle without the action of the autocrine growth factor loop.
Raf-1 protein is required for growth factor-induced proliferation of hematopoietic cells
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TLDR
It is shown that Raf-1 and Ras cooperate in trans-activation through the oncogene-responsive element and that the cysteine-rich region is necessary for this effect.
The effect of c-raf antisense oligonucleotides on growth factor-induced proliferation of hematopoietic cells.
TLDR
Raf-1 is required to transduce growth factor-induced proliferative signals in factor-dependent progenitor cells lines for all known classes of hematopoietic growth factor receptors, and is required for the growth of normal murine and human bone marrow-derived progenitors.
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TLDR
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TLDR
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.
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TLDR
The results lead to the conclusion that Raf-1 protein kinase is a downstream component of this oncogenic signal cascade shared by EGF and PDGF.
Inhibition of v-raf-dependent c-fos expression and transformation by a kinase-defective mutant of the mitogen-activated protein kinase Erk2
TLDR
Results provide compelling evidence that phosphorylation of TCF/Elk-1 by Erk2 is a major link in the Raf-1 kinase-dependent signal transduction pathway that activates c-fos expression.
Differential abilities of activated Raf oncoproteins to abrogate cytokine dependency, prevent apoptosis and induce autocrine growth factor synthesis in human hematopoietic cells
TLDR
Observations indicate that the aberrant expression of certain activated ΔRaf:ER oncoproteins can alter the cytokine dependency of human hematopoietic TF-1 cells.
Complementation of Defective Colony-Stimulating Factor 1 Receptor Signaling and Mitogenesis by Raf and v-Src
TLDR
The ability of oncogenes such as Raf and v-Src to regulate the expression of these proteins reveals new lines of communication between cytosolic signal transducers and the cell cycle machinery.
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TLDR
Findings suggest that proliferative signals generated at the membrane result in the phosphorylation of the Raf-1 protein and the activation of its serine/threonine-specific kinase activity, which may serve to transduce signals from the membrane to the cytoplasm and perhaps on to the nucleus.
Insulin activates the Raf-1 protein kinase.
Effect of a dominant inhibitory Ha-ras mutation on mitogenic signal transduction in NIH 3T3 cells
TLDR
The results suggest that ras proteins are involved in at least two parallel mitogenic signal transduction pathways, one of which is independent of protein kinase C.
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TLDR
Data from immunoprecipitation analysis with raf-specific sera are consistent with a model in which lack of amino-terminal sequences in the c-raf gene product p48raf may, in and of itself, suffice to make it a transforming protein.
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TLDR
The results show that transformation by three growth factor receptor-like oncogenes depends on c-ras proteins, while transformation by two cytoplasmic onCogenes appears to be independent ofc-ras protein.
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TLDR
While RAF‐1 is not a direct substrate for the CSF‐1 receptor tyrosine kinase in vivo, its temperature dependent phosphorylation and activation represent an intriguing aspect of the CSf‐1 response.
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TLDR
Oncogenic activation of the Raf kinase can be achieved by removal of CR1 and CR2 or by steric distortion and requires retention of an active kinase domain, consistent with a protein structure model for the nonstimulated enzyme in which the active site is buried within the protein.
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TLDR
The results suggest that ras proteins are involved in at least two different pathways of signal transduction from the NGF receptor, which can be distinguished by differential sensitivity to p21(Asn-17)Ha-ras.
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