PMID- 10498616
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20061115
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 94
IP  - 7
DP  - 1999 Oct 1
TI  - M-Ras, a widely expressed 29-kD homologue of p21 Ras: expression of a
      constitutively active mutant results in factor-independent growth of an
      interleukin-3-dependent cell line.
PG  - 2433-44
AB  - M-Ras, a recently identified homologue of p21 Ras, is widely expressed, with
      levels of the 29-kD protein in spleen, thymus, and NIH 3T3 fibroblasts equaling
      or exceeding those of p21 Ras. A G22V mutant of M-Ras was constitutively active
      and its expression in an interleukin-3 (IL-3)-dependent mast cell/megakaryocyte
      cell line resulted in increased survival in the absence of IL-3, increased growth
      in IL-4, and, at high expression levels, in factor-independent growth. Expression
      of M-Ras G22V, however, had a negative effect on growth in the presence of IL-3, 
      suggesting that M-Ras has both positive and negative effects on growth.
      Expression of M-Ras G22V in NIH-3T3 fibroblasts resulted in morphological
      transformation and growth to higher cell densities. M-Ras G22V induced activation
      of the c-fos promoter, and bound weakly to the Ras-binding domains of Raf-1 and
      RalGDS. Expression of a mutant of M-Ras G22V that was no longer membrane-bound
      partially inhibited (40%) activation of the c-fos promoter by N-Ras Q61K,
      suggesting that M-Ras shared some, but not all, of the effectors of N-Ras. An
      S27N mutant of M-Ras, like the analogous H-Ras S17N mutant, was a dominant
      inhibitor of activation of the c-fos promoter by constitutively active Src Y527F,
      suggesting that M-Ras and p21 Ras shared guanine nucleotide exchange factors and 
      are likely to be activated in parallel. Moreover, M-Ras was recognized by the
      monoclonal anti-Ras antibody Y13-259, commonly used to study the function and
      activity of p21 Ras. Mammalian M-Ras and a Caenorhabditis elegans orthologue
      exhibit conserved structural features, and these are likely to mediate activation
      of distinctive signaling paths that function in parallel to those downstream of
      p21 Ras.
FAU - Ehrhardt, G R
AU  - Ehrhardt GR
AD  - The Biomedical Research Centre, University of British Columbia, Vancouver, BC,
      Canada.
FAU - Leslie, K B
AU  - Leslie KB
FAU - Lee, F
AU  - Lee F
FAU - Wieler, J S
AU  - Wieler JS
FAU - Schrader, J W
AU  - Schrader JW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Epitopes)
RN  - 0 (Interleukin-3)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.6.1.- (Mras protein, mouse)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - AIM
SB  - IM
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Antibodies
MH  - Cell Division/drug effects/*physiology
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Culture Media, Conditioned
MH  - Epitopes/analysis/immunology
MH  - Humans
MH  - Interleukin-3/*pharmacology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Molecular Weight
MH  - Monomeric GTP-Binding Proteins/chemistry/*genetics/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Proto-Oncogene Proteins p21(ras)/chemistry
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Alignment
MH  - Tumor Cells, Cultured
EDAT- 1999/09/25 00:00
MHDA- 1999/09/25 00:01
CRDT- 1999/09/25 00:00
PHST- 1999/09/25 00:00 [pubmed]
PHST- 1999/09/25 00:01 [medline]
PHST- 1999/09/25 00:00 [entrez]
PST - ppublish
SO  - Blood. 1999 Oct 1;94(7):2433-44.