Focal Adhesion Kinase and the MAPK pathway

In summary, the conversation discusses the activation of the MAPK pathway and the role of FAK in this process. The first image presented shows a simplified model for EGFR signaling, while the second image shows a more complex picture with different inputs and outputs for different MAPK pathways. The conversation also mentions the difficulty in understanding this information and the confusion caused by specialized terms and outdated resources. The main question posed is how exactly FAK activates the MAPK pathway and what it binds to in this process. The request is for a simple and direct explanation of the connection between FAK and the MAPK pathway.
  • #1
Matt204823545
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TL;DR Summary
How exactly does FAK influence the MAPK pathway?
1592014363729.png

The above image (source) is pretty much the only thing we're told about how the MAPK pathway is activated. However, in passing, FAK was mentioned. We were told that focal adhesion integrins activate FAK which then activates the MAPK pathway. Seen in the image (source) below
1592014555948.png


However the two images seem very contradictory. Not only that, but if you Ctrl-F for "fak" or "focal adhesion kinase" on MAPL/ERK pathway (wiki), NOTHING comes up!? On the FAK wiki page "MAPK" isn't mentioned, and "mitogen" is vaguely mentioned in a way that is difficult for me (2nd year biomedicine) to fully understand.

I don't see how FAK can fit into the model I learned in the first image above. I've seen many answers to this but they're all vague and seem to contradict one another.
 
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  • #2
In biology, signal transduction is a very complicated subject and all signaling pathways can have a number of different inputs and outputs. The first image you present is a very simplified model for EGFR signaling showing how activation of the EGF receptor leads to downstream activation of MAP kinases. However, EGFR is not the only signal that can activate MAP kinase pathways. Indeed, there a number of different MAP kinases in cells, so of course there will be different inputs and outputs for distinct MAP kinases. For example, here's an image from a review that emphasizes the different inputs/outputs of different MAPK pathways inside of cells:
1592016236425.png

https://www.sciencedirect.com/science/article/pii/S0167488910003228

Most diagrams presented in biology textbooks and papers will be simplifications that don't capture everything that occurs in reality. Also, I have found that for more advanced topics in biology, Wikipedia is not the best resource as it can often be out of date. The best resource for looking more information on MAPK or FAK signaling pathways would be to look up primary research articles or reviews published in scientific journals.
 
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Likes BillTre and jim mcnamara
  • #3
You didn't mention FAK at all other than to direct me to go read articles and journals that I don't comprehend in the slightest, I told you I'm only a 2nd year undergraduate student (with low marks). I tried reading many articles and journals but 99.99999% of the information there is useless for me as they say nothing about how FAK is connected to MAPKKK and the terms are all specialised and confusing and I don't have a lifetime to find the answer to this 1 question.
The image you provided does not have FAK on it, hence it's utterly useless for me.

Once again, I ask: How exactly does FAK activate the MAPK pathway? What does FAK bind, what does that then lead to, etc.

Please just tell me in simple straight-to-the-point terms exactly how FAK is connected to the MAPK pathway.
 

1. What is Focal Adhesion Kinase (FAK)?

Focal Adhesion Kinase (FAK) is a protein that plays a crucial role in cell adhesion and migration. It is involved in the formation and maintenance of focal adhesions, which are specialized structures that connect the cell to the extracellular matrix. FAK also plays a role in signaling pathways that regulate cell growth, survival, and differentiation.

2. How does FAK interact with the MAPK pathway?

FAK can activate the MAPK pathway by phosphorylating and activating the protein Src, which then activates the MAPK pathway. FAK can also directly interact with components of the MAPK pathway, such as the proteins MEK and ERK, to regulate their activity. This crosstalk between FAK and the MAPK pathway plays a critical role in cell proliferation, survival, and migration.

3. What is the significance of the MAPK pathway in cancer?

The MAPK pathway is frequently dysregulated in cancer, leading to abnormal cell growth and proliferation. FAK is also overexpressed and hyperactivated in many types of cancer, and its interaction with the MAPK pathway can contribute to tumor growth and metastasis. Therefore, targeting FAK and the MAPK pathway has become a promising strategy for cancer treatment.

4. How is the activity of FAK and the MAPK pathway regulated?

The activity of FAK and the MAPK pathway is tightly regulated by various mechanisms. FAK can be activated by integrin-mediated cell adhesion and growth factor signaling. On the other hand, the MAPK pathway can be activated by various extracellular stimuli, such as growth factors and stress signals. Additionally, negative regulators, such as phosphatases, can inhibit the activity of FAK and the MAPK pathway to maintain balance in cellular signaling.

5. What are the potential therapeutic implications of targeting FAK and the MAPK pathway?

As mentioned earlier, dysregulation of FAK and the MAPK pathway is associated with various diseases, including cancer. Therefore, targeting these pathways has become a promising approach for therapeutic intervention. Several inhibitors have been developed to target FAK and the MAPK pathway, and they are currently being evaluated in clinical trials for the treatment of cancer and other diseases.

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