Isoform-specific localization of A-RAF in mitochondria.

RAF kinase is a family of isoforms including A-RAF, B-RAF, and C-RAF. Despite the important role of RAF in cell growth and proliferation, little evidence exists for isoform-specific function of RAF family members. Using Western analysis and immunogold labeling, A-RAF was selectively localized in highly purified rat liver mitochondria. Two ...
novel human proteins, which interact specifically with A-RAF, were identified, and the full-length sequences are reported. These proteins, referred to as hTOM and hTIM, are similar to components of mitochondrial outer and inner membrane protein-import receptors from lower organisms, implicating their involvement in the mitochondrial transport of A-RAF. hTOM contains multiple tetratricopeptide repeat (TPR) domains, which function in protein-protein interactions. TPR domains are frequently present in proteins involved in cellular transport systems. In contrast, protein 14-3-3, an abundant cytosolic protein that participates in many facets of signal transduction, was found to interact with C-RAF but not with A-RAF N-terminal domain. This information is discussed in view of the important role of mitochondria in cellular functions involving energy balance, proliferation, and apoptosis and the potential role of A-RAF in regulating these systems.
Mesh Terms:
14-3-3 Proteins, Amino Acid Sequence, Animals, Biological Transport, Blotting, Western, Carrier Proteins, Humans, Membrane Proteins, Mitochondria, Liver, Mitochondrial Proteins, Molecular Sequence Data, Protein Isoforms, Proteins, Proto-Oncogene Proteins c-raf, Rats, Recombinant Fusion Proteins, Repetitive Sequences, Amino Acid, Sequence Homology, Amino Acid, Two-Hybrid System Techniques, Tyrosine 3-Monooxygenase
Mol. Cell. Biol.
Date: Jul. 01, 2000
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