Ras-GRF Activates Ha-Ras, but Not N-Ras or K-Ras 4B, Proteinin Vivo *

@article{Jones1998RasGRFAH,
  title={Ras-GRF Activates Ha-Ras, but Not N-Ras or K-Ras 4B, Proteinin Vivo *},
  author={Michael K. Jones and Janis H. Jackson},
  journal={The Journal of Biological Chemistry},
  year={1998},
  volume={273},
  pages={1782 - 1787}
}
Human cells contain four homologous Ras proteins, but it is unknown whether these homologues have different biological functions. As a first step in determining if Ras homologues might participate in distinct signaling cascades, we assessed whether a given Ras guanine nucleotide exchange factor could selectively activate a single Ras homologue in vivo. We found that Ras-GRF/Cdc25Mm activates Ha-Ras, but does not activate N-Ras or K-Ras 4B, protein in vivo. Moreover, our results suggested that… 

Figures from this paper

Four Human Ras Homologs Differ in Their Abilities to Activate Raf-1, Induce Transformation, and Stimulate Cell Motility*
TLDR
The results indicate that the four Ras homologs significantly differ in their abilities to activate Raf-1 and induce distinctly different biological responses, and suggest for the first time that the distinct and likely cooperative biological functions of the Ki-ras-encoded Ki-Ras 4A and Ki- Ras 4B proteins may help explain why constitutively activating mutations of Ki-ra, but not N-ras or Ha-ras, are frequently detected in human carcinomas.
Ras-Gefs and Ras Gaps
TLDR
This review analyzed new mechanisms of Rac activation due to covalent-interaction with hydrophobic molecules as NO and cyclopentenone prostaglandins and focused on the possible physiological specificities of each Ras-GAP/Ras-GEF family member.
M-Ras/R-Ras3, a Transforming Ras Protein Regulated by Sos1, GRF1, and p120 Ras GTPase-activating Protein, Interacts with the Putative Ras Effector AF6*
TLDR
These findings suggest that while M-Ras is regulated by similar upstream stimuli to Ha-RAS, novel targets may be responsible for its effects on cellular transformation and differentiation.
The Ras-GRF1 exchange factor coordinates activation of H-Ras and Rac1 to control neuronal morphology.
TLDR
Results suggest that coordinated activation of H-Ras and Rac1 by Ras-GRF1 may be a significant controller of neuronal cell size.
Differences on the Inhibitory Specificities of H-Ras, K-Ras, and N-Ras (N17) Dominant Negative Mutants Are Related to Their Membrane Microlocalization*
TLDR
The results on Ras N17 mutants specificities exhibit a marked correlation with the localization of the Ras isoforms to distinct membrane microdomains, and are presented for the first time a description of N-Ras cellular microlocalization.
Sensitivity of wild type and mutant ras alleles to Ras specific exchange factors: Identification of factor specific requirements
TLDR
The H-Ras mutant V103E, which is competent for membrane localization, nucleotide binding, intrinsic and stimulated GTPase activity as well as intrinsic exchange, was defective for activation by all factors tested, suggesting the integrity of this residue is necessary for catalyzed exchange.
Distinct Mechanisms Determine the Patterns of Differential Activation of H-Ras, N-Ras, K-Ras 4B, and M-Ras by Receptors for Growth Factors or Antigen
TLDR
The molecular mechanisms leading to activation of Ras proteins vary with the stimulus and can be influenced by either colocalization with activated receptors or differential sensitivity to the exchange factors activated by a stimulus.
Phosphorylation of the Ras-GRF1 Exchange Factor at Ser916/898 Reveals Activation of Ras Signaling in the Cerebral Cortex*
TLDR
It is demonstrated here that Ras-GRF1 is highly expressed in rat brain compared with the Sos exchange factor and that there is an increase in incorporation of 32P into Ser898 of brain Ras- GRF1 following activation of protein kinase A.
Two Ras Pathways in Fission Yeast Are Differentially Regulated by Two Ras Guanine Nucleotide Exchange Factors
TLDR
It is proposed that external signals can partly segregate two Ras1 pathways by modulating GEF expression and that GEFs can influence how Ras is coupled to specific effectors.
Stimulation of Ras Guanine Nucleotide Exchange Activity of Ras-GRF1/CDC25Mm upon Tyrosine Phosphorylation by the Cdc42-regulated Kinase ACK1*
TLDR
It is shown here that activated ACK1, a nonreceptor tyrosine kinase that belongs to the focal adhesion kinase family, causes tyosine phosphorylation of Ras-GRF1 and suggest a signaling cascade consisting of Cdc42, ACK 1, Ras- GRF1, and Ras in neuronal cells.
...
...

References

SHOWING 1-10 OF 48 REFERENCES
Differential response of the Ras exchange factor, Ras-GRF to tyrosine kinase and G protein mediated signals.
TLDR
The results suggest that Ras-GRF has the capacity to mediate Ras activation initiated by signals using heterotrimeric G proteins.
Vav cooperates with Ras to transform rodent fibroblasts but is not a Ras GDP/GTP exchange factor.
TLDR
Vav can cooperate with normal Ras proteins to transform NIH3T3 cells and results suggest that Vav and Ras may mediate signal transduction by distinct, but interactive mitogenic pathways.
Calcium activation of Ras mediated by neuronal exchange factor Ras-GRF
TLDR
It is shown that the ability of Ras-GRF to activate Ras in vivo is markedly enhanced by raised Ca2+ concentrations, which implicate Ras- GRF in the regulation of neuronal functions that are influenced by Ca2-influx signals.
Identification of residues of the H-ras protein critical for functional interaction with guanine nucleotide exchange factors.
TLDR
Evidence is presented that the mechanism by which CDC25 catalyzes exchange is more involved than simply catalyzing the release of bound nucleotide and passively allowing nucleotides to rebind and suggests a function for CDC25 in promoting the selective exchange of GTP for GDP.
Involvement of the Switch 2 Domain of Ras in Its Interaction with Guanine Nucleotide Exchange Factors (*)
TLDR
It is reported that mutations within the switch 2 domain of Ras (residues 62-69) inhibit activation of Ras by the mammalian GEFs, Sos1, and GRF/CDC25.
Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21
TLDR
The cloning of complementary DNAs from a rat brain library that encode a ∼140 GRF for Ras p21 (p140Ras-GRF) is reported, which accelerated the release of GDP from RasH and RasN p21 in vitro, but not from the related RalA, or CDC42Hs GTP-binding proteins.
Phosphorylation-dependent activation of the Ras-GRF/CDC25Mm exchange factor by muscarinic receptors and G-protein βγ subunits
TLDR
It is reported that muscarinic receptors can activate another Ras exchange factor, CDC25Mm, or p140Ras-GRF, and a G-protein-coupled mechanism for Ras activation is demonstrated, mediated by p140RAF.
Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2.
TLDR
The results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex consisting of GRB2 and hSos1, a guanine nucleotide exchange factor for Ras.
Dbl and Vav mediate transformation via mitogen-activated protein kinase pathways that are distinct from those activated by oncogenic Ras.
TLDR
Observations indicate that Vav and Dbl transformation is not a consequence of Ras activation and instead may involve the constitutive activation of MAPKs.
...
...