Rat neuronal leucine-rich repeat protein-3: cloning and regulation of the gene expression.
Rat neuronal leucine-rich repeat protein-3 (rNLRR-3) gene was isolated and cloned from fibrosarcoma cells overexpressing c-Ha-ras. Stable expression of constitutively active forms of Ras (H-Ras(V12) or v-H-Ras) led to a two- to fourfold increase in rNLRR-3 mRNA in rat normal fibroblasts (3Y1). When cells expressing H-Ras(V12) were treated with mitogen activated protein kinase (MAPK) kinase inhibitors (U0126, PD98059), suppression of rNLRR-3 mRNA correlated well with a reduction in MAPK activity. Epidermal growth factor (EGF) led to elevation of rNLRR-3 gene expression about 4 h after stimulation of normal fibroblasts. U0126 completely suppressed the induction by EGF of rNLRR-3 mRNA with abrogation of MAPK phosphorylation. U0126 inhibited the basal transcription of rNLRR-3. LY294002, a PI3 kinase inhibitor, showed a lesser effect on expression of the gene. These results indicate that rNLRR-3 gene expression is regulated mainly through the Ras-MAPK signaling pathway in fibroblasts.
Fukamachi
K
K
Experimental Pathology and Chemotherapy Division, Biophysics Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Matsuoka
Y
Y
Kitanaka
C
C
Kuchino
Y
Y
Tsuda
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D005786:Gene Expression Regulation; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism
D018076:DNA, Complementary; C484458:Lrrn3 protein, rat; D009419:Nerve Tissue Proteins; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins