Ras effectors and their role in mitogenesis and oncogenesis

  title={Ras effectors and their role in mitogenesis and oncogenesis},
  author={Tom Joneson and Dafna Bar-Sagi},
  journal={Journal of Molecular Medicine},
Abstract Ras proteins are membrane-bound GTP-binding proteins that play a critical role in the control of cell growth. Through a large number of genetic and biochemical studies it is becoming increasingly evident that the biological activity of Ras proteins is mediated by multiple signaling pathways. This review provides an account of the target proteins that interact with Ras and the functional consequences of these interactions. The relative contribution of the different Ras effector pathways… 

RAS pathways to cell cycle control and cell transformation.

This review deals with the most recent advances on the role of Ras in the signal transduction pathway from external signals to the cell cycle and gene expression control and addresses the new developments on the effect of Ras activation in the regulation of different molecules driving thecell cycle progression.

Suppression of Ras-Induced Apoptosis by the Rac GTPase

A role for Rac is demonstrated in controlling signals that are necessary for cell survival, and a mechanism by which Rac activity can confer growth advantage to cells transformed by the rasoncogene is suggested.

Raf: a strategic target for therapeutic development against cancer.

The structure and diverse functions of Raf, the rationale for targeting Raf as a therapeutic strategy against cancer, and the present status of various therapeutic approaches including ASONs and small molecules, particularly sorafenib (BAY 43-9006).

The role of mitogen-activated ERK-kinase inhibitors in lung cancer therapy.

  • A. Adjei
  • Biology, Medicine
    Clinical lung cancer
  • 2005
The potential utility of MEK inhibitors in the therapy of lung cancer is discussed and the most promising approach to date appears to be the inhibition of mitogen-activated ERK kinase or MEK.

The Activation of RalGDS Can Be Achieved Independently of Its Ras Binding Domain

Small GTPases of the Ras family are major players of signal transduction in eukaryotic cells. They receive signals from a number of receptors and transmit them to a variety of effectors. The

Requirement of Activated Cdc42-Associated Kinase for Survival of v-Ras-Transformed Mammalian Cells

It is shown that the ACK-1 isoform of ACK plays a critical role in transducing Ras-Cdc42 signals in the NIH 3T3 cells, suggesting that ACK -1 is a novel target for therapies directed at Ras-induced cancer.

Prospects for anti‐ras drugs

New aspects and approaches towards a selective blockade of Ras oncogenicity are illuminated to illuminate new aspects of Ras regulation and signal transduction.

Multiple Ras Downstream Pathways Mediate Functional Repression of the Homeobox Gene Product TTF-1

The data indicate that the Raf/MEK/ERK cascade may act in concert with an as-yet-uncharacterized signaling pathway activated by V12N38 Ras to repress TTF-1 function and ultimately to inhibit thyroid cell differentiation.

Complementation of Defective Colony-Stimulating Factor 1 Receptor Signaling and Mitogenesis by Raf and v-Src

The ability of oncogenes such as Raf and v-Src to regulate the expression of these proteins reveals new lines of communication between cytosolic signal transducers and the cell cycle machinery.



Ras effectors.

  • C. Marshall
  • Biology, Computer Science
    Current opinion in cell biology
  • 1996

Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1

The Ras polypeptide and the amino-terminal regulatory domain of Raf-1 are shown to interact, directly in vitro and in a yeast expression system, and Mutations in and around the Ras effector domain impair Ras binding to Raf- 1(1-257) and Ras transforming activity in parallel.

Inhibition of Ras-induced DNA synthesis by expression of the phosphatase MKP-1.

An essential role for activation of MAP kinases in the transition from the quiescent to the DNA replication phase of the eukaryotic cell cycle is suggested.

Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro

It is reported that the amino-terminal cysteine-rich regulatory region of p74c-raf-1 expressed as a glutathione-S-transferase (GST) fusion protein binds directly to Ras with relatively high affinity (50 nM).

Ras target proteins in eukaryotic cells

  • M. Marshall
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1995
This review will attempt to sum‐marize the current literature of accepted and potential Ras‐dependent signaling proteins in both lower eukaryotes and vertebrates.

Complex formation between RAS and RAF and other protein kinases.

We used a Saccharomyces cerevisiae genetic system to detect the physical interaction of RAS and RAF oncoproteins. We also observed interaction between RAS and byr2, a protein kinase implicated as a

Phosphatidylinositol-3-OH kinase direct target of Ras

In vivo, dominant negative Ras mutant N17 inhibits growth factor induced production of 3′ hosphorylated phosphoinositides in PC12 cells, and transfection of Ras, but not Raf, into COS cells results in a large elevation in the level of these lipids.

Association between GTPase activators for Rho and Ras families

It is shown here that p190 can function as a GAP specifically for members of the rho family, and 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.