Investigation of Phosphoprotein Phosphatases: Structure, Function, and Regulation
Reversible phosphorylation of proteins at Ser, Thr, and Tyr residues is a major control mechanism which regulates most aspects of cell life. The regulation of protein function by phosphorylation requires both protein phosphatases (PPs) and kinase (PKs). PPs are highly regulated. They playcentral and specific role in many cellular processes.

Four major types of protein Ser(p)/Thr(p) phosphatase known: PP-1, -2A, -2B, and -2C. The catalytic subunit of PP-1 is a 38 kDa protein (C1). In cells, C1 associates with different targeting subunits which specify the location, catalytic, and regulatory property of C1. Genetic evidence indicates that PP-1 plays an essential role in mitosis and in other events coupled to cell cycle.

In the nucleus, one of the potential targeting subunit/substrate for PP-1 is retinoblastoma protein (RB). We are studying the role of PP-1 in regulating the phosphorylation state of RB. We have employed the yeast 2-hybrid system to isolate cDNAs encoding proteins able to bind PP-1, with a goal to identify nucleus targeting subunit/substrates of PP-1. Most PP-1 protein exists in cytosol as an inactive form (PP-1i) which requires the action of protein kinase FA for activation. We will study the regulation of PP-1i by PKFA and the relationship between PP-1i and the nucleus form(s) of the enzyme. In addition to PP-1, we also have an interest in studying the function and regulation of protein tyrosine phosphatase-1B.