The aims of the research proposed here are to study the structure of the insulin receptor and the mechanism by which insulin activates membrane transport systems, in particular the (NA+, K+) ATPase and other Na+ transporters.
One aim i s to identify functional domains of the insulin receptor involved in monomer-monomer interactions, disulfide bond formation and insulin binding. Another aim is to determine and isolate the components involved in transducing the signal of the insulin receptor interaction to the (Na+, K+) ATPase and other Na+ transporters.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK027626-06
Application #
3228400
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1981-03-01
Project End
1991-02-28
Budget Start
1986-03-20
Budget End
1987-02-28
Support Year
6
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Wu, James Jianping; Guidotti, Guido (2004) Proreceptor dimerization is required for insulin receptor post-translational processing. J Biol Chem 279:25765-73
Wu, James Jianping; Guidotti, Guido (2002) Construction and characterization of a monomeric insulin receptor. J Biol Chem 277:27809-17
Lee, K; Jung, J; Kim, M et al. (2001) Interaction of the alpha subunit of Na,K-ATPase with cofilin. Biochem J 353:377-85
Chen, W; Guidotti, G (2001) Soluble apyrases release adp during ATP hydrolysis. Biochem Biophys Res Commun 282:90-5
Coppi, M V; Compton, L A; Guidotti, G (1999) Isoform-specific effects of charged residues at borders of the M1-M2 loop of the Na,K-ATPase alpha subunit. Biochemistry 38:2494-505
Coppi, M V; Guidotti, G (1997) The alpha2L111R,N122D isoform of the Na,K-ATPase expressed in HeLa cells does not undergo an adipocyte-like increase in activity in response to insulin. Biochem Biophys Res Commun 236:444-8
Coppi, M V; Guidotti, G (1997) Intracellular localization of Na,K-ATPase alpha2 subunit mutants. Arch Biochem Biophys 346:312-21
Coppi, M V; Guidotti, G (1997) Ubiquitination of Na,K-ATPase alpha1 and alpha2 subunits. FEBS Lett 405:281-4
Santy, L C; Guidotti, G (1997) Expression of a single gene produces both forms of skeletal muscle cyclic nucleotide-gated channels. Am J Physiol 273:E1140-8
Santy, L C; Guidotti, G (1996) Reconstitution and characterization of two forms of cyclic nucleotide-gated channels from skeletal muscle. Am J Physiol 271:E1051-60

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