Access Type

Open Access Thesis

Date of Award

January 2014

Degree Type


Degree Name



Pharmaceutical Sciences

First Advisor

Zhengping Yi


Protein Phosphatase 1 (PP1), a member of Serine/ Threonine Phosphatase family, targets its dephosphorylation activity on serine and threonine residues. As the catalytic subunit of PP1, PP1c can achieve its substrate specificity only by binding with PP1 regulatory subunits. Previous researches have shown that PP1c can involve in multiple functional regulation by associating with various interaction partners. Since serine/ threonine phosphorylation on the Insulin receptor substrate-1 (IRS1) may direct inactivation and degradation of IRS1, this phosphorylation activity is believed to be a source of Insulin Resistance. PP1 is hypothesized to dephosphorylate serine/ threonine site on IRS1, which may rescue the Insulin resistance.

However, the PP1c interaction partners involve in this process is unclear, and little is known about the proteins that interact with PP1c in humans in health conditions. We used a proteomic approach to assess PP1c interaction partners in skeletal muscle from lean healthy participants before and after insulin infusion. As a result, we identified 46 novel endogenous PP1c interaction partners which consist of the largest PP1c interactome in human skeletal muscle and become new targets for studies of PP1c complexes in various diseases. Furthermore, we identified 8 proteins show significantly changes after insulin treatment. These novel PP1c interactions provide new insights into the molecular mechanism of insulin action and identify new targets for further PP1c researches in Type 2 Diabetes.