Two human cDNAs, including a homolog of Arabidopsis FUS6 (COP11), suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction in yeast and mammalian cells.
We have isolated two novel human cDNAs, gps1-1 and gps2, that suppress lethal G-protein subunit-activating mutations in the pheromone response pathway of the yeast Saccharomyces cerevisiae. Suppression of other pathway-activating events was examined. In wild-type cells, expression of either gps1-1 or gps2 led to enhanced recovery from cell cycle arrest induced by pheromone. Sequence analysis indicated that gps1-1 contains only the carboxy-terminal half of the gps1 coding sequence. The predicted gene product of gps1 has striking similarity to the protein encoded by the Arabidopsis FUS6 (COP11) gene, a negative regulator of light-mediated signal transduction that is known to be essential for normal development. A chimeric construct containing gps1 and FUS6 sequences also suppressed the yeast pheromone pathway, indicating functional conservation between these human and plant genes. In addition, when overexpressed in mammalian cells, gps1 or gps2 potently suppressed a RAS- and mitogen-activated protein kinase-mediated signal and interfered with JNK activity, suggesting that signal repression is part of their normal function. For gps1, these results are consistent with the proposed function of FUS6 (COP11) as a signal transduction repressor in plants.
Spain
B H
BH
Department of Biological Chemistry and Molecular Biology Institute, UCLA School of Medicine, Los Angeles, California 90095, USA.
Bowdish
K S
KS
Pacal
A R
AR
Staub
S F
SF
Koo
D
D
Chang
C Y
CY
Xie
W
W
Colicelli
J
J
D000595:Amino Acid Sequence; D000818:Animals; D029681:Arabidopsis Proteins; D000075686:COP9 Signalosome Complex; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008322:Mammals; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000235:genetics*; D011506:Proteins; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics*
D029681:Arabidopsis Proteins; C086322:CSN1 protein, Arabidopsis; D018076:DNA, Complementary; D005656:Fungal Proteins; C103315:GPS1 protein, human; C103316:GPS2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D010940:Plant Proteins; D011506:Proteins; D012097:Repressor Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000075686:COP9 Signalosome Complex; D019204:GTP-Binding Proteins