KSR, a novel protein kinase required for RAS signal transduction.
We have identified and characterized two genes in Drosophila whose products are required for activated RAS to signal with normal efficiency, but do not appear to effect signaling by activated RAF. One encodes the beta subunit of type I geranylgeranyl transferase, a prenylation enzyme essential for targeting RAS to the plasma membrane. The other encodes a protein kinase that we have named kinase suppressor of ras (ksr). By genetic criteria, we show that KSR functions in multiple receptor tyrosine kinase pathways. We have isolated mammalian homologs of KSR that, together with the Drosophila gene, define a novel class of kinases. Our results suggest that KSR is a general and evolutionarily conserved component of the RAS signaling pathway that acts between RAS and RAF.
Therrien
M
M
Howard Hughes Medical Institute, University of California, Berkeley 94720-3200, USA.
Chang
H C
HC
Solomon
N M
NM
Karim
F D
FD
Wassarman
D A
DA
Rubin
G M
GM
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000201:enzymology / Q000235:genetics; D005260:Female; D017344:Genes, Insect / Q000235:genetics; D016153:Genes, Suppressor / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017956:Photoreceptor Cells, Invertebrate / Q000254:growth & development; D012150:Polymorphism, Restriction Fragment Length; D011494:Protein Kinases / Q000235:genetics* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D014166:Transferases / Q000235:genetics*; D018631:ras Proteins / Q000502:physiology*
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; C095279:Rab geranylgeranyl transferase beta-subunit; D014166:Transferases; D011494:Protein Kinases; C097199:KSR-1 protein kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C080148:tor protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D018631:ras Proteins