Molecular cloning of cDNAs encoding the GAP-associated protein p190: implications for a signaling pathway from ras to the nucleus.
In mitogenically stimulated and tyrosine kinase-transformed cells, a substantial fraction of the ras GTPase-activating protein (GAP) forms a complex with a protein termed p190. We have cloned several cDNAs encoding the p190 protein. Analysis of the predicted protein sequence reveals three distinct domains with homology to previously described sequences. An N-terminal domain of p190 contains sequence motifs that are found in all of the known GTPases. At the C-terminus of the protein is a domain that contains sequences very similar to those found in the breakpoint cluster region gene product, n-chimerin, and rho GAP, all of which have been shown to possess intrinsic GAP activity on small GTPases. Finally, a 778 aa segment in the middle of p190 is nearly identical in sequence to a recently described transcriptional repressor. This raises the possibility that p190, acting via GAP, can transduce signals from p21ras to the nucleus, perhaps affecting expression of specific cellular genes.
Settleman
J
J
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
Narasimhan
V
V
Foster
L C
LC
Weinberg
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D015870:Gene Expression; D020662:Guanine Nucleotide Exchange Factors; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010750:Phosphoproteins / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000737:chemistry; D015183:Restriction Mapping; D016415:Sequence Alignment; D015398:Signal Transduction; 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; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D020703:ras GTPase-Activating Proteins; D004247:DNA; D016283:Proto-Oncogene Proteins p21(ras)