Understanding the Sequence Requiremet for the PHTH Domain Dimerization of BTK from Phylogenetic Analysis

Neema, V. (2019) Understanding the Sequence Requiremet for the PHTH Domain Dimerization of BTK from Phylogenetic Analysis. Masters thesis, Indian Institute of Science Education and Research Kolkata.

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Abstract

Bruton's Tyrosine Kinase (Btk), a Tec family non-receptor tyrosine kinase is essential for the B-cell signalling. Recent studies shows that Btk can be activated in a membrane independent pathway, where inositol hexakisphosphate (IP6) helps in the transient dimerization of the PHTH domain in solution. Though PHTH domain is common in all Tec family kinases, only Btk is known to dimerize in the presence of IP6. Through phylogenetic analysis of Btk, we found that an 18 residue sequence is present only in Btk of mammals and a few other vertebrates. This loop region might play an important in the IP6 mediated dimerization of Btk. To test this hypothesis, we tried to establish a system using Btk WT and E41K in presence of IP6.

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