Interference of mannose 6-phosphate/insulin-like growth factor II receptor function by interactions with cancer-associated minireceptors

BIOL 216

Jodi L. Kreiling, jkreiling@mail.unomaha.edu1, Jennifer L. Kopanic, jkopanic@mail.unomaha.edu1, Michelle A. Hartman, mahartman@unmc.edu2, and Richard G. MacDonald, rgmacdon@unmc.edu2. (1) Department of Chemistry, University of Nebraska at Omaha, 6001 Dodge St, Omaha, NE 68182, (2) Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198
The mannose 6-phosphate/insulin-like growth factor II receptor (Man6P/IGF2R) is a multifunctional protein involved in lysosome formation, cell growth regulation, and suppression of cancer formation. Association of two normal Man6P/IGF2Rs into a dimer is critical for optimal function. Two receptor mutations predicted to produce shortened forms of the Man6P/IGF2R have been reported in gastrointestinal and hepatocellular tumors. The hypothesis guiding this work is that in cells the presence of these smaller receptors with the normal Man6P/IGF2R leads to the formation of broken receptor complexes, creating abnormal dimers that would have reduced functional activity and/or stability and potentially lead to cancer progression. Cotransfection assays reveal instability of the normal Man6P/IGF2R protein when expressed with increasing concentrations of the shortened receptors. Immunoprecipitation assays also indicate that weak dimeric complexes develop between the normal and shortened forms of the Man6P/IGF2R. The following studies will further investigate the mechanisms of this effect.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007