The G beta gamma sensitivity of a PI3K is dependent upon a tightly associated adaptor, p101.
Two highly similar, PtdIns(4,5)P2-selective, G beta gamma-activated PI3Ks were purified from pig neutrophil cytosol. Both were heterodimers, were composed of a 101 kDa protein and either a 120 kDa or a 117 kDa catalytic subunit, and were activated greater than 100-fold by G beta gammas. Peptide sequence-based oligonucleotide probes were used to clone cDNAs for the p120 and p101 species. The cDNA of p120 is highly related to p110 gamma, while the cDNA of p101 is not substantially related to anything in current databases. The proteins were expressed in and purified from insect and mammalian cells. They bound tightly to one another, both in vivo and in vitro, and in so doing, p101 amplified the effect of G beta gammas on the PI3K activity of p120 from less than 2-fold to greater than 100-fold.
Stephens
L R
LR
Department of Signalling, The Babraham Institute, Cambridge, United Kingdom.
Eguinoa
A
A
Erdjument-Bromage
H
H
Lui
M
M
Cooke
F
F
Coadwell
J
J
Smrcka
A S
AS
Thelen
M
M
Cadwallader
K
K
Tempst
P
P
Hawkins
P T
PT
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003600:Cytosol / Q000737:chemistry; D018076:DNA, Complementary; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007313:Insecta; D015473:Leukemia, Promyelocytic, Acute; D008322:Mammals; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D012680:Sensitivity and Specificity; D013552:Swine; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000201:enzymology
D018076:DNA, Complementary; D011994:Recombinant Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D019204:GTP-Binding Proteins