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Lesli-Hunnicutt

Page history last edited by lfhunnic@edisto.cofc.edu 13 years, 2 months ago

 

 

Ras protein

 

The 'choreographer' of cell life- (Baylor 

 

 

 

I. Basic information

 

It is a signal transduction protein that regulates and controls intracellular signaling networks by converting signals from the cell membrane to the nucleus(Wikipedia).  It is part of the Ras superfamily encompassing 8 other subfamilies in which all share the common G core providing GTPase activity(Wikipedia). Ras proteins control cell migration, proliferation, differentiation, cell adhesion, and apoptosis(Wikipedia).

 


 II. How Ras works

 

 

 

The protein is associated with the plasma membrane where it binds to either GDP or GTP acting as a molecular switch(Tufts University). When Ras is GDP bound, it is in the inactive state or the off position (Tufts University). It is activated by guanine nucleotide exchange factors (GEF) at the plamsa membrane that take the GDP off and replace it with a GTP (Pathfinder ; webhost). When it is GTP bound, Ras is active and able to activate other proteins(Tufts University). The protein itself has a natural inability to return from its active form back to its inactive form and it requires the help of the GTPase-activating protein or GAP (Tufts University).

 

 

This figure shows the on and off states for Ras. For a bigger image: (et al. biologie

 

         Ras and Signal Pathways 

One single Ras protein can be involed in multiple signal pathways and regulate completely different functions. The question researchers wish to answer is how one protein regulates multpile factors and knows which process to activate(Chang). This is leading to theories that Ras is involved with compartment specific signaling (Chang). 

 

An example of Ras in a pathway results in the transcription of genes involved in cell growth and division in which the mitogen-activated protein (MAP) kinase cascade has been well-studied. (Wikipedia-protein)

 

Ras in a general transduction pathway:  

http://porpax.bio.miami.edu/~cmallery/150/gene/c7.19.12a.Ras.jpg 

 

 


 III. Mutations in Ras

 There are 3 similar Ras proteins, present in mammalian speices, that are consider to be oncogenic (ncbi/rasoncogenes). Oncogenes are genes that when mutated help to turn a normal cell into a canerous cell (Wikipedia-oncogenes). Ras, when it was originally found, was thought to be the oncogene resonsible for the cancer-causing activity in the Harvey and Kirsten murine sarcoma viruses (Der Lab). It was then found that a mutation in the normal protein produces its oncogenic form (Singer). The Ras proteins that mostly undergo mutations are (ncbi/rasoncogenes):

 

 

K-Ras- This protein mutates most often and the mutations mostly occur in pancreatic and colon cancers.

 

N-Ras- Mutations mostly prevalent in melanoma, liver cancer, and luekemia.

 

H-Ras- Mutations occur in bladder, kidney, and thyroid carcinomas

 

 

 Mutations in the ras genes can permanently activate the protein resulting in incorrect signaling inside the cell(ncbi/rasoncogenes). Pancreatic cancer has been highly linked to Ras protein mutations in which 90% of pancreatic tumors contain a mutation in the K-ras gene(ncbi/rasoncogenes ; cancer research). Colon cancer has also been highly linked in which 50% of colon tumors have an Ras mutation(ncbi/rasoncogenes). Even though K-Ras is the type most commonly mutated in colon cancer, not all colon tumors have a mutation in K-Ras. RASAL1, an Ras regulator, has also been found to be linked to tumor progression (RASAL1).

 


 IV. Cancer Therapy  

 

Since there is a high correlation between certain types of cancer and the Ras mutation, cancer therapy has been focused on developing anti-cancer drugs to act on the Ras protein (Oxford Journals). Three major approaches have been taken:

     1) Inhibition of Ras Expression

     2) Inhibition of Ras Membrane Localization

     3) Interruption of Signaling Pathways downstream of Ras(Oxford Journals).

 

 

 

 

 

 

 

 

 

Comments (1)

Christopher Korey said

at 10:31 pm on Apr 6, 2009

You are very close here. Expand the paragraphs a bit with a little more detail, but then most of the work will be in referencing and linking out to the papers or more detailed information. You want to provide a path for further exploration. Keep the headings as you have them and divide each section with a horizontal line for clarity. Remember to reference the material like any other paper.

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