Methods to inhibit serine kinase activity and to alter intersubu

Details Methods to inhibit serine kinase activity and to alter intersubu Methods to inhibit serine kinase activity and to alter intersubu

1994-01-21

1998-04-21

Patterson, Jr., Charles L.

Chemistry: molecular biology and microbiology

Enzyme , proenzyme; compositions thereof; process for...

Transferase other than ribonuclease

43524027, 4352523, 4353201, 4241391, 530 241, 536 231, 536 241, C12N 912

Patent

active

057416893

ABSTRACT:
The invention provides for a method to inhibit the binding between the p85 and p110 subunits of said PI3-kinase and thus a method to modulate PI3-kinase activity and modulate the response of cells to external stimuli. In particular, disabling, by conventional means, residues located in the inter-SH2 domain of said p85 subunit, specifically a region containing amino acid residue 478 to amino acid residue 513 of p85.alpha. subunit, or amino acid residue 445 to amino acid residue 485 of p85.beta. subunit of said PI3-kinase. Interference with these binding regions will affect binding between the subunits and results in inhibiting PI3-kinase activity. This invention further relates to a methods to modulate the serine kinase activity of the PI3-kinase which can be achieved by disabling the DRHNSN sequence of the p110 subunit and can also be used to effect changes in overall PI3-kinase activity. This invention is further related to an (ant)agonist which affects serine kinase activity of PI3-kinase. An agonist is provided which stimulates the phosphorylation of the p85 subunit at the serine residue at position 608, wherein phosphorylation at the serine residue indirectly results in inhibiting PI3-kinase activity.

REFERENCES:
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Dhand, et al, "EBMO Journal vol. 13, No. 3, 511-521, 1994, "PI 3-kinase: structural and functional analysis of inter-subunit interactions.
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