Association between GTPase activators for Rho and Ras families.
The ras-related low-molecular-mass GTPases participate in signal transduction involving a variety of cellular functions, including cell-cycle progression, cellular differentiation, cytoskeletal organization, protein transport and secretion. The cycling of these proteins between GTP-bound and GDP-bound states is partially controlled by GTPase activating proteins (GAPs) which stimulate the intrinsic GTP-hydrolysing activity of specific GTPases. The ras GTPase-activating protein (Ras-GAP) forms a complex with a second protein, p190 (M(r) 190,000), in growth-factor stimulated and tyrosine-kinase transformed cells. At its carboxy-terminal end, p190 contains a region that is conserved in the breakpoint cluster region, n-chimaerin, and Rho-GAP. Each of these three proteins exhibits GAP activity for at least one member of the rho family of small GTPases. We have tested recombinant p190 protein for GAP activity on GTPases of the ras, rho and rab families, and show here that p190 can function as a GAP specifically for members of the rho family. Consequently, the formation of a complex between Ras-GAP and p190 in growth-factor stimulated cells may allow the coupling of signalling pathways that involve ras and rho GTPases.
Settleman
J
J
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
Albright
C F
CF
Foster
L C
LC
Weinberg
R A
RA
D000818:Animals; D004268:DNA-Binding Proteins; D020558:GTP Phosphohydrolases / Q000502:physiology*; D020690:GTPase-Activating Proteins; D005786:Gene Expression Regulation; D011905:Genes, ras / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors; D007313:Insecta / Q000235:genetics; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000502:physiology; D010750:Phosphoproteins / Q000302:isolation & purification / Q000502:physiology; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000502:physiology; D051381:Rats / Q000235:genetics; D012097:Repressor Proteins; D012234:Rho Factor / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection; D020703:ras GTPase-Activating Proteins
C513040:Arhgap35 protein, rat; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D012097:Repressor Proteins; D012234:Rho Factor; D020703:ras GTPase-Activating Proteins; D020558:GTP Phosphohydrolases