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Columnar epithelial cells from the colonic mucosa are studied to identify abnormalities in cell signaling pathways. Abnormal epithelial cells from colonic adenocarcinoma are shown to have a mutation that blocks hydrolysis of GTP-bound active RAS. Normal columnar cells have active RAS protein that undergoes hydrolysis to the inactive GDP-bound form. Which of the following signaling pathways is most likely abnormally stimulated in the carcinoma cells?

a. Jak-Stat Pathway
b. MAP kinase pathway
c. p53
d. Both a & b

I think its MAP kinase pathway because RAS is part of MAP kinase pathway that ultimately leads to transcription and expression of genes but if GTP is not hydrolyzed then RAS will be constantly activated leading to continued gene expression that may lead to cancer but I am not completely sure about it because p53 is also a tumor suppressor gene.

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Is this a homework/test question? It looks a lot like one. –  Jeremy Kemball Jul 10 at 18:42
    
Homework questions are off-topic unless you show some effort of solving them yourself. What are your thoughts about it? –  Chris Jul 10 at 18:44
    
Hi, this very much sounds like a homework question! It will be great if you show some evidence of what you think the likely answer is and why so that any input would be constructive! –  Bez Jul 10 at 18:46
    
I think it is MAP kinase pathway because if GTP is not hydrolyzed then it will lead to constant activation of RAS as RAS is in MAP kinase pathway..so what is your opinion..? –  emi Jul 10 at 19:15
    
Perhaps also take a look at Jak-stat and see what pathways influences it! and as correctly mentioned p53 is an inhibitor so it can't be the right answer! –  Bez Jul 11 at 15:12
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2 Answers 2

It is both, a and b. The JAK-STAT-Pathway sits below the Erb-receptor and is therefore giving the signal from mutated Erb down the signalling cascade. Besides that a permanent active version of Jak2 has been found which also permanently activates this pathway. Both are contributing to cancer. See this two articles:

The role of the MAP Kinase pathway in cancer is even more prominent. Mutations in different proteins of the cascade are know, like BRAF V6600E in melanoma, mutations in NRAS, KRAS, MEK and MEK2. Most of these are activating mutations which lead to a permanent activation of this signalling cascade and also a changed gene expression. See this figure from the MAP Kinase paper mentioned below:

enter image description here

See these papers for more details:

p53 is not a signalling pathway, but a single protein which plays an important role in the regulation of the cell cycle and is important in the prevention of tumors. It is also called a "tumor suppressor gene" and is often mutated or deactivated in cancer. For more details on p53 see here.

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Whoever downvoted my answer, what is your problem with it? I can (and will) improve it, when you can tell what you think is wrong with it. –  Chris Jul 21 at 10:05
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i thnk it is MAP Kinase pathway b'coz RAS is a protein involved in this pathway and mutation in it lead to permanent attachment of GTP leading to cell proliferation causing carcer

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We're looking for long answers that provide some explanation and context. Don't just give a one-line answer; explain why your answer is right, ideally with citations. Answers that don't include explanations may be removed.

    
Can you please work out your answer? At the moment this is more a comment. –  Chris Jul 12 at 15:59
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