Identification and characterization of R-ras3: a novel member of the RAS gene family with a non-ubiquitous pattern of tissue distribution

被引:74
作者
Kimmelman, A
Tolkacheva, T
Lorenzi, MV
Osada, M
Chan, AML
机构
[1] CUNY MT SINAI SCH MED,DERALD H RUTTENBERG CANC CTR,NEW YORK,NY 10029
[2] NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892
关键词
Ras; TC21; R-ras; G-protein; transformation; MAPK;
D O I
10.1038/sj.onc.1201674
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Members of the Ras subfamily of GTP-binding proteins, including Ras (H-, K-, and N-), TC21, and R-ras have been shown to display transforming activity, and activating lesions have been detected in human tumors. We have identified an additional member of the Ras gene family which shows significant sequence similarity to the human TC21 gene. This novel human ras-related gene, R-rad, encodes for a protein of 209 amino acids, and shows similar to 60-75% sequence identity in the N-terminal catalytic domain with members of the Ras subfamily of GTP-binding proteins. An activating mutation corresponding to the leucine 61 oncogenic lesion of the ras oncogenes when introduced into R-ras3, activates its transforming potential. R-ras3 weakly stimulates the mitogen-activated protein kinase (MAPK) activity, but this effect is greatly potentiated by the co-expression of c-raf-l. By the yeast two-hybrid system, R-rad interacts only weakly with known Ras effecters, such as Raf and RalGDS, but not with RglII. In addition, R-ras3 displays modest stimulatory effects on trans-activation from different nuclear response elements which bind transcription factors, such as SRF, ETS/TCF, Jun/Fos, and NF-kappa B/Rel. Interestingly, Northern blot analysis of total RNA isolated from various tissues revealed that the 3.8 kilobasepair (kb) transcript of R-rad is highly restricted to the brain and heart. The close evolutionary conservation between R-rad and Ras family members, in contrast to the significant differences in its biological activities and the pattern of tissue expression, raise the possibility that R-rad may control novel cellular functions previously not described for other GTP-binding proteins.
引用
收藏
页码:2675 / 2685
页数:11
相关论文
共 54 条
[1]   CHARACTERIZATION OF A GUANINE-NUCLEOTIDE DISSOCIATION STIMULATOR FOR A RAS-RELATED GTPASE [J].
ALBRIGHT, CF ;
GIDDINGS, BW ;
LIU, J ;
VITO, M ;
WEINBERG, RA .
EMBO JOURNAL, 1993, 12 (01) :339-347
[2]  
BOS JL, 1989, CANCER RES, V49, P4682
[3]  
CHAN AML, 1994, P NATL ACAD SCI USA, V82, P2394
[4]   THE SMALL GTP-BINDING PROTEINS RAC1 AND CDC42 REGULATE THE ACTIVITY OF THE JNK/SAPK SIGNALING PATHWAY [J].
COSO, OA ;
CHIARIELLO, M ;
YU, JC ;
TERAMOTO, H ;
CRESPO, P ;
XU, NG ;
MIKI, T ;
GUTKIND, JS .
CELL, 1995, 81 (07) :1137-1146
[5]   ACTIVATION OF MAP KINASE KINASE IS NECESSARY AND SUFFICIENT FOR PC12 DIFFERENTIATION AND FOR TRANSFORMATION OF NIH 3T3 CELLS [J].
COWLEY, S ;
PATERSON, H ;
KEMP, P ;
MARSHALL, CJ .
CELL, 1994, 77 (06) :841-852
[6]  
COX AD, 1994, ONCOGENE, V9, P3281
[7]  
DER CJ, 1991, CANCER CELL-MON REV, V3, P331
[8]   OVEREXPRESSION OF THE HUMAN EGF RECEPTOR CONFERS AN EGF-DEPENDENT TRANSFORMED PHENOTYPE TO NIH 3T3 CELLS [J].
DIFIORE, PP ;
PIERCE, JH ;
FLEMING, TP ;
HAZAN, R ;
ULLRICH, A ;
KING, CR ;
SCHLESSINGER, J ;
AARONSON, SA .
CELL, 1987, 51 (06) :1063-1070
[9]   CHARACTERIZATION OF 4 NOVEL RAS-LIKE GENES EXPRESSED IN A HUMAN TERATOCARCINOMA CELL-LINE [J].
DRIVAS, GT ;
SHIH, A ;
COUTAVAS, E ;
RUSH, MG ;
DEUSTACHIO, P .
MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (04) :1793-1798
[10]   Ras interaction with two distinct binding domains in Raf-1 may be required for Ras transformation [J].
Drugan, JK ;
KhosraviFar, R ;
White, MA ;
Der, CJ ;
Sung, YJ ;
Hwang, YW ;
Campbell, SL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (01) :233-237