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Many essential signaling processes in animal cells are mediated by enzymes that phosphorylate and dephosphorylate tyrosine residues on proteins as a means of relaying information. These enzymes, known as protein tyrosine kinases and protein tyrosine phosphatases, play a crucial role in normal animal physiology and are often dysregulated in diseases such as cancers and immunological disorders. As a result, these enzymes are important drug targets.
There are ~100 members of the tyrosine kinase and tyrosine phosphatase families, and we are inspired by the evolution of the complex signaling networks that they control. Our goal is to integrate chemical approaches with high-throughput biochemical assays, biophysical methods, and evolutionary analyses to pinpoint (1) how individual members of these enzyme families have specialized to mediate signal transduction with fidelity, (2) how the dysregulation of phosphotyrosine signaling enzymes leads to disease states, and (3) how we might exploit this information to guide the development of novel therapies.
There are ~100 members of the tyrosine kinase and tyrosine phosphatase families, and we are inspired by the evolution of the complex signaling networks that they control. Our goal is to integrate chemical approaches with high-throughput biochemical assays, biophysical methods, and evolutionary analyses to pinpoint (1) how individual members of these enzyme families have specialized to mediate signal transduction with fidelity, (2) how the dysregulation of phosphotyrosine signaling enzymes leads to disease states, and (3) how we might exploit this information to guide the development of novel therapies.
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David C. Cabanero,Stavros K. Kariofillis,Andrew C. Johns, Jinwoo Kim, Jizhi Ni, Sangho Park,Dann L. Parker,Carlo P. Ramil,Xavier Roy,Neel H. Shah,Tomislav Rovis
JOURNAL OF THE AMERICAN CHEMICAL SOCIETYno. 2 (2024): 1337-1345
Anne E van Vlimmeren,Rashmi Voleti,Cassandra A Chartier, Ziyuan Jiang,Deepti Karandur, Preston A Humphries, Wan-Lin Lo,Neel H Shah
biorxiv(2024)
PROTEIN SCIENCEno. 12 (2023)
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Journal of Biological Chemistryno. 3 (2023): 104179-S637
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bioRxiv : the preprint server for biology (2023)
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PROTEIN SCIENCEno. 12 (2023)
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Yuan-Li Tsai, Marcel Arias-Badia,Theresa A. Kadlecek, Yee May Lwin, Aahir Srinath,Neel H. Shah,Zhi-En Wang,Diane Barber, John Kuriyan,Lawrence Fong,Arthur Weiss
IMMUNITYno. 12 (2023): 2682-2698.e9
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