The present invention relates to the discovery, identification and characterization of nucleotides that
encode the
G protein regulated
phosphatidylinositol-3'
kinase, a heterodimeric
enzyme which produces the
intracellular messenger
phosphatidylinositol (3,4,5)-triphosphate in response to activation of trimeric
G protein-linked receptors. This
novel protein, comprised of a catalytic
subunit, p120, and a regulatory
subunit, p101, is found in cells of hematopoietic origin and is involved in
immune system responses which cause
inflammation. The presence of p101
subunit is largely responsible for the dramatic stimulation of
kinase activity in the presence of activated trimeric G proteins. The invention encompasses p101 and p120 nucleotides; host
cell expression systems, p101 and p120 proteins, fusion proteins, polypeptides and peptides, antibodies to these proteins, transgenic animals that express a p101 or p120
transgene, or recombinant knock-out cells and animals that do not express the p101 or p120
gene, antagonists and agonists of the
enzyme, and other compounds that modulate p101 or p120
gene expression or
enzyme activity that can be used for diagnosis,
drug screening,
clinical trial monitoring, and / or the treatment of inflammatory disorders.