This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What are protein interaction networks?
Proteins interact with one another to form complex pathways that aid in things like gene expression and cellular communication. Without protein interactions, the machinery in each of our cells would be useless. The interactions can be as simple as direct binding to as complex as a signaling pathway, and that's why interaction networks exist. They allow us to visualize the relationships among proteins.
The circular images are the proteins themselves, for example, TGFB1. The thickness of the lines connecting the proteins indicates the certainty that they are in fact interacting.
Proteins can interact with each other directly, or indirectly. Signaling pathways, like those involving TGFB1, are generally a sequence of direct protein interactions. However, the initial protein and the final protein that are affected may never directly interact with one another. Losrtan, a medicine that acts as an angiotensin ii receptor antagonist, is able to decrease TGFB1 expression. The drug itself, nor the protein it acts on, never directly interact with TGFB1. This is why the study of interaction networks is integral to understanding TGFB1 and allergic rhinitis.
The following webs are interaction networks in various organisms. Different organisms can sometimes have different names for the same homologus gene, so they are labeled at the top of each network.
The circular images are the proteins themselves, for example, TGFB1. The thickness of the lines connecting the proteins indicates the certainty that they are in fact interacting.
Proteins can interact with each other directly, or indirectly. Signaling pathways, like those involving TGFB1, are generally a sequence of direct protein interactions. However, the initial protein and the final protein that are affected may never directly interact with one another. Losrtan, a medicine that acts as an angiotensin ii receptor antagonist, is able to decrease TGFB1 expression. The drug itself, nor the protein it acts on, never directly interact with TGFB1. This is why the study of interaction networks is integral to understanding TGFB1 and allergic rhinitis.
The following webs are interaction networks in various organisms. Different organisms can sometimes have different names for the same homologus gene, so they are labeled at the top of each network.
What does TGFB1 interact with in humans?
Angiotensin ii receptor: AGTR1
TGFB1: TGFB1
In humans, the AGTR1 protein interacts with TGFB1 through AGT and APP.
TGFB1: TGFB1
In humans, the AGTR1 protein interacts with TGFB1 through AGT and APP.
Zebra Fish
Angiotensin ii receptor: LOC794575
TGFB1: tgfb1a
In zebra fish, the angiotensin ii receptor interacts with tgfb1a through pparg, and agt. Agt is also one of the protein intermediates in humans for this interaction. A noteworthy protein here is tnfb. Tnfb, or tumor necrosis factor beta, is another inflammatory cytokine in the immune system. It is interesting that the zebra fish homolog to the antiotensin ii receptor also indirectly interacts with tnfb.
TGFB1: tgfb1a
In zebra fish, the angiotensin ii receptor interacts with tgfb1a through pparg, and agt. Agt is also one of the protein intermediates in humans for this interaction. A noteworthy protein here is tnfb. Tnfb, or tumor necrosis factor beta, is another inflammatory cytokine in the immune system. It is interesting that the zebra fish homolog to the antiotensin ii receptor also indirectly interacts with tnfb.
Mice
Angiotensin ii receptor: Agtr1a
TGFB1: tgfb1
In mice, the angiotensin ii receptor interacts with tgfb1 indirectly through agt and app. These are the same two protein intermediates in the human interaction of these two proteins. Mice also share some sequential interactions with humans like Smad proteins and other tgfb proteins.
TGFB1: tgfb1
In mice, the angiotensin ii receptor interacts with tgfb1 indirectly through agt and app. These are the same two protein intermediates in the human interaction of these two proteins. Mice also share some sequential interactions with humans like Smad proteins and other tgfb proteins.
Fruit Flies
Angiotensin ii receptor: AlCR2
TGFB1: Dawdle
In fruit flies, the interaction is extremely different than in the other three model organisms above. The angiotensin ii receptor protein homolog is not interacting closely with dawdle, the drosophila's version of TGFB1. There are interactions that could lead to the relationship of the two, but they take a lot of distant interactions. This could be because of how different the drosophila immune system is. Drosophila have no adaptive immune system, and they have an open circulatory system. An open circulatory system contains hemolymph instead of blood, and there are not blood vessels in the same sense that humans have blood vessels. For this reason, drosophila can be used as an excellent negative comparison for TGFB1 and how it functions in immunity. Similarities between species who share immune systems, especially when different from drosophila, could be hypothesized to be the features of TGFB1 necessary for immune function.
TGFB1: Dawdle
In fruit flies, the interaction is extremely different than in the other three model organisms above. The angiotensin ii receptor protein homolog is not interacting closely with dawdle, the drosophila's version of TGFB1. There are interactions that could lead to the relationship of the two, but they take a lot of distant interactions. This could be because of how different the drosophila immune system is. Drosophila have no adaptive immune system, and they have an open circulatory system. An open circulatory system contains hemolymph instead of blood, and there are not blood vessels in the same sense that humans have blood vessels. For this reason, drosophila can be used as an excellent negative comparison for TGFB1 and how it functions in immunity. Similarities between species who share immune systems, especially when different from drosophila, could be hypothesized to be the features of TGFB1 necessary for immune function.
Analysis
Narrowing in on the pathway that TGFB1 uses to interact with Losartan and the angiotensin ii receptor is important to understanding how the drug can help to decrease the levels of TGFB1. The interaction is slightly different in the model organisms whose networks are laid out above. Although zebra fish aren't an exact copy of the human interaction network, the main indirect interaction between TGFB1 and the angiotensin ii receptor is intact. Fruit flies however are a different story, their interaction network is significantly different from the other three. These similarities and differences can be used to highlight the parts in the pathway that are important for TGFB1 immune function, and the function of Losartan on the expression levels of TGFB1. The drug Losartan targets the angiotensin ii receptor protein and thus decreases the levels of TGFB1, and we can see via protein interaction networks how that process may occur.
References
[1] Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015;43:D447–52. doi: 10.1093/nar/gku1003
Images
[1] http://www.iscb.org/cms_addon/conferences/ismb2014/artscience.php
Images
[1] http://www.iscb.org/cms_addon/conferences/ismb2014/artscience.php