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Comments for assignment 3

Submitted by cdkelly on Thu, 10/18/2018 - 23:42

It's really interesting that fusion proteins can be expressed. I assumed that Abl did something to the protein that it fused with in the cytosol, like affect its noncovalent bonding and consequently change its conformation/function. But, this implies that the fusion protein is expressed so the mutation begins at the DNA before transcription.

Does the Abl kinase act as a phosphatase? It states that one of its functions is to inhibit tyrosine kinases. Maybe it acts as a competitor for phosphorylation as a mechanism of inhibition instead?  

This is fascinating because I assumed that all SH2 domains functioned as phosphotyrosine binding partners. But in the case of Abl, it seems that the SH2 domain functions to bind to the SH3 domain and thereby maintain its autoinhibition. If the SH2 domain is not able to bind to a phosphorylated tyrosine, then its normal function will no longer work.

This facet of Abl 1b coincides with its cancerous tendencies. If the kinase activity is deregulated then the implications for the cell as a whole are not good. Cancerous cell utilize these kinds of mutations for grow and proliferate. Without normal regulation, the kinase can promote this. Therefore, it makes sense that the Abl 1b mutant is commonly a part of the cell that when mutated can lead to cancer.

Since Gab/Grb2 fulfill such a large role in the cell, it makes sense that its deregulation by Bcr-Abl results from the mutation. Gab/Grb2 bind to epidermal growth factor receptors (EGFR) which is a commonly mutated in various forms of cancer. Furthermore, because Gab2 serves a number of other functions in the cell like being the binding site for the assembly of SHP2 and potentially coordinating STAT5, its deregulation can have serious consequences for the longevity of the cell.

 

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