|The balance between phosphorylation
and dephosphorylation of signaling molecules is crucial for living organisms to maintain their
normal physiological functions. Deregulation of signaling pathways that results in disturbing
this balance often leads to the development of diseases such as cancer. Indeed, elevated Akt
signaling is commonly associated with a variety of human cancers as the result of
hyperphosphorylation of its downstream substrates. We have recently identified a novel protein
phosphatase PHLPP, which specifically antagonizing Akt function by directly dephosphorylating
Akt and triggering apoptosis. The research focus of my lab is to understand the molecular
mechanisms underlying the regulation of PHLPP and to elucidate the role of PHLPP in the
tumorigenesis process. The lab combines biochemical, molecular and cell biological and genetic
approaches to pursue the following research interests: 1) characterizing how PHLPP is regulated
at the cellular and molecular levels; 2) identifying novel targets of PHLPP; and 3) elucidating
the role of PHLPP as a tumor suppressor using transgenic animal models.
Gao T, Furnari F, and Newton AC. PHLPP: a Phosphatase that Directly
Dephosphorylates Akt, Promotes Apoptosis, and Suppresses Tumor Growth. Mol. Cell 18:13-24,
Gao T, Newton AC. The turn
motif is a phosphorylation switch that regulates the binding of Hsp70 to protein kinase C.
J Biol Chem 277:31585-92, 2002. Epub 2002 Jun 21.
Sonnenburg ED, Gao T, Newton AC. The phosphoinositide-dependent kinase, PDK-1,
phosphorylates conventional protein kinase C isozymes by a mechanism that is independent of
phosphoinositide 3-kinase. J Biol Chem 276:45289-97, 2001. Epub 2001 Sep 28.
Gao T, Toker A, Newton AC.
The carboxyl terminus of protein kinase c provides a switch to regulate its interaction with
the phosphoinositide-dependent kinase, PDK-1. J Biol Chem 276:19588-96, 2001. Epub 2001