Events -- Beta Cell Interest Group (BIG)

MafA Activity is Regulated by Phosphorylation

Shuangli Guo
Postdoctoral Fellow
Stein Lab

MafA is a highly phosphorylated transcription factor, which was originally isolated due to its association with Insulin gene expression. The analysis of the MafA knockout has established an importance in islet β cells, as adult mutant mice are hyperglycemic due to a deficiency in insulin secretion. Work from this laboratory and others suggests that phosphorylation of MafA is critical to function, by (at least) influencing DNA- and activation-potential. Mass spectrometry and kinase consensus site strategies were used here to identify sites of amino acid phosphorylation. Our data has demonstrated that phosphorylation at serine 65 (i.e. S65) influences both the stability and trans-activation potential of MafA. Interestingly, phosphomimetic replacement mutants at S65 show a differential role in these responses. Thus, the glutamic acid (E) mutant behaved like phosphoserine and was also ubiquitinated and unstable, while aspartic acid (D) and alanine (A) mutants were stable and poorly modified. In contrast, both the S65E and S65D mutants stimulated trans-activation. Our results not only point to the central role of S65 phosphorylation to MafA activity, but also illustrate the differential sensitivity of the transcriptional and protein degradation machinery to acidic amino replacement mutants at this site.

About this ongoing activity:

The Vanderbilt Center for Stem Cell Biology (VCSCB) sponsors a weekly Beta Cell Interest Group (BIG) meeting for invited Vanderbilt faculty, research assistants and students to discuss topics relating to beta cell biology. BIG meetings are held on Wednesdays from 9:00-10:00 AM in 512 Light Hall.