Anti-PI3K, p110α: Rabbit Anti-Phosphoinositide 3-kinase, p110α Antibody

BACKGROUND PI3 kinase (EC 2.7.1.137) belongs to a family of lipid kinases which catalyze the phosphorylation at the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). PI-3 kinase activities have been found to be are linked to an incredibly diverse set of key cellular functions, including cell growth, proliferation, motility, differentiation, survival and intracellular trafficking.¹ It was also involved in human maladies, including allergy, inflammation, heart disease and cancer. Inhibitors of these enzymes are considered potential therapeutic agents.²

 

PI3 kinase family members are grouped into three classes according to their sequence homologies and substrate specificities. Class Ia PI3K is a heterodimer consisting of a catalytic subunit, p110 (three isoforms p110 alpha, beta, and delta), and an associated regulatory subunit, so called p85 (p85 alpha, p85 beta and p55 gamma isoforms, two splicing variants p55 alpha and p50 alpha from p85 alpha).  In vitro, the catalytic subunit phosphorylates PtdIns at the D3 position of their inositol ring to produce PI3P, PI-3, 4-P2 and PI-3,4,5-P3.  In contrast to class Ia PI3K which is activated by receptor tyrosine kinases, class Ib PI3K generates PIP3 upon activation of G-protein coupled receptors. Class Ib PI3K also consists of a regulatory subunit (p101) and a catalytic subunit (p110gamma).³

 

Class II PI3K contains a C-terminal region with homology to C2 domains and has therefore been termed PI3KC2. PI3KC2 isoforms (alpha, beta, gamma) produce mainly PI3P and PI-3,4-P2 in vitro, although human PI3KC2alpha converts PI-4,5-P2 to PIP3 in the presence of phosphatidylserine. There is evidence that PI3KC2 isoforms are also activated upon PDGF, insulin and EGF.  Class II PI 3-kinases have not been isolated in association with a regulatory subunit, but they possess extended N- and C-termini relative to the class I PI 3-kinases, which may serve this function.⁴

 

Class III PI 3-kinases are exemplified by the sole Saccharomyces cerivisiae PI 3-kinase, Vps34.  Unlike class I and II PI 3-kinases, this enzyme can phosphorylate only PtdIns and is thus a PtdIns 3-kinase. All eukaryotes investigated have a single Vps34 homologue. The human gene (PIK3C3) is located on chromosome 18 at 18q12.3. A single 150 kDa regulatory subunit (in yeast VPS15, in humans PIK3R4, located at 3q22.1) possesses intrinsic protein-serine kinase activity that is required for Vps34 function. Total cellular levels PI3P levels do not change much upon growth factor stimulation. Class III PI3K is involved in diverse intracellular trafficking events including autophagy and phagosome formation, internal vesicle formation within multivesicular endosomes, retrograde endosome to Golgi transport and transport at the nuclear membrane.⁵
 

REFERENCES  

1. Foster, F.M. et al: J. Cell Sci. 116:3037-3040, 2003
2. Ward, S.G. & Finan, P.: Curr. Opin. Pharm. 3:426-434, 2003
3. Wu, H. et al: Biochem Soc Trend. 35:242-244, 2007
4. Traer, C.J. et al: Bull. Cancer 93:E53-58, 2006
5. Backer, J.M.: Biochem. J. 410:1-17, 2008