Document Sample
Appl Powered By Docstoc
					                      APPL, an AKT2-Interacting Protein

Dr. Joseph Testa, Dr. Mitsuuchi, and colleagues at Fox Chase Cancer Center, using the
yeast two hybrid method, first identified APPL, a potential regulatory protein for the
serine/threonine kinase, AKT2, which may have significant implications for cancer study
and treatment.

The Akt family of kinases is involved in many cellular processes, such as proliferation
and survival. AKT2 is prominent during mitosis and is over-expressed in a subset of
human ovarian and pancreatic cancers. Thus, AKT2 may have a significant impact on
cell cycle progression. APPL (Adaptor protein containing a Pleckstrin homology
domain, a Phosphotyrosine binding domain, and a Leucine zipper motif) interacts with
AKT2 through its PTB (phosphotyrosine binding) domain, and its role may include an
adaptor molecule function. It is postulated that APPL may be involved in enhancing the
cell signaling events important for mitosis because it allows for physical communication
between AKT2 and p110, the catalytic subunit of phosphatidylinositiol 3-kinase, at the
plasma membrane during cell division. APPL is highly expressed in tissues expressing
abundant AKT2, such as the ovary, pancreas; skeletal muscle, and heart. Importantly,
disruption of APPL protein expression has been shown to activate apoptosis and has
demonstrated effectiveness toward reducing the aggressiveness and progression of cancer

Cancer Research-APPL antibodies may be utilized in animal models of cancer in order
to study APPL’s effects on cancer development and progression.
Cancer Drug Analysis and Development-In addition, APPL antibodies can be coupled to
other chemotherapeutic agents, such as cisplatin and taxol, which interfere with tumor
growth, establishment, and metastasis. Also, wild-type and truncated APPL cDNA
constructs can be applied to microarray technology to examine how changes in
expression levels of APPL affect response to cancer medications, especially ovarian and
pancreatic treatments. Furthermore, the APPL gene and protein may represent potential
targets for cancer drug design.

APPL polyclonal antibodies and APPL cDNA constructs are available for licensing.

Patent Status
A U.S. patent application has been filed.
                       For further information please contact:

                                     Frances Galvin
                                   Assistant Director
                            Office of Business Development
                               Fox Chase Cancer Center
                                 333 Cottman Avenue
                                Philadelphia, PA 19111
                                  Tel: (215) 728-1113
                                  Fax: (215) 214-1440

                           About Fox Chase Cancer Center

Fox Chase Cancer Center is an independent, not-for-profit institution devoted to cancer
treatment and prevention, clinical research, and basic research on cancer prevention,
initiation, and progression. More than 150 clinical trials are typically ongoing at any
time. Key discoveries of Fox Chase researchers include the Scid mouse and the Hepatitis
B vaccine. Fox Chase was one of the first institutes to be designated as a comprehensive
cancer center by the National Cancer Institute and remains among the top three NCI-
core grant recipients in the country. Fox Chase is a founding member of the National
Comprehensive Cancer Network, an alliance of the world’s leading cancer centers, and
has a network of hospital affiliations in Pennsylvania, New Jersey and Delaware.

Shared By: