Partner exchange: protein-protein interactions in the Raf pathway.
The three-tiered Raf-MEK-ERK kinase module is activated downstream of Ras and has been traditionally linked to cellular proliferation. Mammals have three Raf, two Mek and two Erk genes. Recently, the analysis of protein-protein interactions in the pathway has begun to provide a rationale for the redundancy within each tier. New results show that the MEK-ERK-activating unit consists of Raf hetero- and homodimers; downstream of Raf, MEK1-MEK2 heterodimers and ERK dimers are required for temporal and spatial pathway regulation. Finally, C-Raf mediates pathway crosstalk downstream of Ras by directly binding to and inhibiting kinases engaged in other signaling cascades. Given the roles of these interactions in tumorigenesis, their study will provide new opportunities for molecule-based therapies that target the pathway.
Wimmer
Reiner
R
University of Vienna, Center for Molecular Biology, Max F. Perutz Laboratories, Doktor-Bohr-Gasse 9, A-1030 Vienna, Austria.
Baccarini
Manuela
M
D000818:Animals; D019281:Dimerization; D005246:Feedback; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D015398:Signal Transduction; D048490:raf Kinases / Q000378:metabolism*
D048490:raf Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020930:MAP Kinase Kinase Kinases