Active survival domains of IGF-IR and methods of use

Details Active survival domains of IGF-IR and methods of use Active survival domains of IGF-IR and methods of use

1996-04-01

1999-09-28

Teng, Sally P.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 3, 530300, 530350, 530399, 530402, 435 691, 435194, C07K 1400, C12N 1509, C12N 1552

Patent

active

059588721

ABSTRACT:
Active Survival Domains in the Insulin-like Growth Factor-I Receptor (IGF-IR) required for transmitting the survival signal in vertebrate cells have been identified. In FL5.12 cells transfected with wild type IGF-I receptors, IGF-I provided protection from IL-3 withdrawal analogous to the protection afforded by expression of Bcl-2. Under the same conditions, IGF-I did not have a significant mitogenic effect on FL5.12 cells expressing IGF-I receptors. An IGF-I receptor with a mutation at the ATP-binding site did not provide protection from apoptosis. However, mutations at tyrosine residue 950 or in the tyrosine cluster (1131, 1135, and 1136) in the kinase domain resulted in receptors that retained survival function. In the C-terminus of the IGF-IR, mutation at tyrosine 1251 and at histidine 1293 and lysine 1294 abolished apoptotic function, whereas mutation of the four serines at 1280-1283 did not affect survival. Surprisingly, receptors truncated at the C-terminus had enhanced anti-apoptotic function. The compositions and methods of the invention are useful for modulating apoptosis in vertebrate cells.

REFERENCES:
Burgaud et al., Biochem. Biophys. Res. Commun., 214, 475-481, Sep. 14, 1995.
Miura et al., J. Biological Chemistry, 270, 22639-22644, Sep. 22, 1995.

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