Disease relevance of c-raf

• However, only c-raf-1 occurs naturally in truncated versions, such as v-raf and v-mil in the acutely transforming retroviruses 3611-MSV and MH2. raf transformation can also be affected by point mutation, suggesting that this mechanism may activate c-raf-1 as an oncogene in carcinogenesis [1].

High impact information on c-raf

• R-ras interacts with rasGAP, neurofibromin and c-raf but does not regulate cell growth or differentiation [2].
• Nucleotide sequence of Xenopus C-raf coding region [3].
• Cells expressing a dominant negative mutant of Raf protein kinase exhibited markedly reduced sensitivity to both LPA and IGF-I, consistent with a role for endogenous Raf in glucose uptake by both growth factors [4].
• Furthermore, we discovered that c-raf induces oocyte maturation that is inhibited by glutathione-S-transferase (GST), which we have found to be a potent and selective inhibitor of JNK [5].
• We have previously found that a ras switch 1 domain peptide (PNC-7, residues 35-47) selectively blocks oocyte maturation induced by oncogenic (Val 12-containing) ras-p21 protein and also blocks c-raf-induced oocyte maturation [6].

Biological context of c-raf

• Xenopus c-raf proto-oncogene: cloning and expression during oogenesis and early development [7].
• raf oncogenes in carcinogenesis [1].
• We conclude that PNC-7 blocks ras by binding to the amino-terminal domain of raf and that raf BXB must initiate signal transduction in the cytosol [6].
• To determine what raf-dependent but MAPK-independent pathway is activated by wild-type ras-p21, we have analyzed gene expression in oocytes induced to mature either with oncogenic ras-p21 or with insulin using a newly available Xenopus gene array [8].

Anatomical context of c-raf

• METHODS: We microinjected raf dominant negative mutant mRNA (DN-raf) and the MEK-specific phosphatase, MKP-T4, either together with oncogenic p21 or c-raf mRNA, into oocytes or into oocytes incubated with insulin to determine the effects of these raf-MEK-MAP kinase pathway inhibitors [5].

Analytical, diagnostic and therapeutic context of c-raf

• PURPOSE: We have previously found that microinjection of activated MEK (mitogen activated kinase kinase) and ERK (mitogen-activated protein; MAP kinase) fails to induce oocyte maturation, but that maturation, induced by oncogenic ras-p21 and insulin-activated cell ras-p21, is blocked by peptides from the ras-binding domain of raf [5].

References