Potent transforming activity of the small GTP-binding protein Rit in NIH 3T3 cells: evidence for a role of a p38gamma-dependent signaling pathway.
A novel branch of the Ras family, Rit, was recently identified. Rit exhibits a distinct C-terminus and effector domain, and does not activate mitogen-activated protein kinase (MAPK) but can cooperate with Raf to transform fibroblasts. Here, we found that when overexpressed, activated mutants of Rit transform NIH 3T3 cells efficiently, and stimulate p38gamma but not MAPK, p38alpha, p38gamma, p38delta, or ERK5. Furthermore, we provide evidence that p38gamma activation is required for the ability of Rit to stimulate gene expression and cellular transformation. These findings suggest that this unique GTPase stimulates proliferative pathways distinct from those regulated by other Ras family members.
Sakabe
Kaoru
K
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4330, USA.
Teramoto
Hidemi
H
Zohar
Muriel
M
Behbahani
Babak
B
Miyazaki
Hiroshi
H
Chikumi
Hiroki
H
Gutkind
J Silvio
JS
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D003599:Cytoskeleton / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016758:Genes, jun / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; D020935:MAP Kinase Signaling System; D051379:Mice; D048291:Mitogen-Activated Protein Kinase 12; D048054:Mitogen-Activated Protein Kinase 7; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010802:Phylogeny; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D048291:Mitogen-Activated Protein Kinase 12; D011505:Protein-Tyrosine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases; D048371:MAP Kinase Kinase 3; C482531:Map2k3 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases; D020558:GTP Phosphohydrolases; C472865:Rit1 protein, mouse; D018631:ras Proteins