TY - JOUR
T1 - Isoform-specific localization of A-RAF in mitochondria
AU - Yuryev, Anton
AU - Ono, Makoto
AU - Goff, Stephen A.
AU - Macaluso, Frank
AU - Wennogle, Lawrence P.
PY - 2000/7
Y1 - 2000/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034092329&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034092329&partnerID=8YFLogxK
U2 - 10.1128/MCB.20.13.4870-4878.2000
DO - 10.1128/MCB.20.13.4870-4878.2000
M3 - Article
C2 - 10848612
AN - SCOPUS:0034092329
SN - 0270-7306
VL - 20
SP - 4870
EP - 4878
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 13
ER -