Enzymes
Product List
p85a Bovine
Phosphoinositide 3-kinase a, regulatory subunit Bovine Recombinant
PI3Ka Bovine
Phosphoinositide 3-kinase alpha p110a/p85a Bovine Recombinant
PI3Kb Human
Phosphoinositide 3-kinase beta p110β/p85α Human Recombinant
PI3Kd Human
Phosphoinositide 3-kinase p110d/p85a Human Recombinant
PI3KγD946GST Human
Phosphoinositide 3-kinase p110γ inactive mutant Human Recombinant
The PI3KγD946GST protein is a catalytically inactive mutant of PI3Kγ with a D946A mutation in the ATP binding site. This recombinant catalytically inactive protein can be used as a negative control in any kind of PI3Kγ kinase activity studies. Recombinant full length PI3KgDA mutant (126.3 kDa without Tag) carries an N-terminal GST-Tag which facilitates the protein’s application in typical GST pull-down assays.
Introduction
Phosphoinositide 3-kinases (PI3Ks), also known as phosphatidylinositol 3-kinases, are a family of enzymes involved in various cellular functions such as cell growth, proliferation, differentiation, motility, survival, and intracellular trafficking . PI3Ks are capable of phosphorylating the 3’ position hydroxyl group of the inositol ring of phosphatidylinositol . The PI3K family is divided into four classes based on primary structure, regulation, and in vitro lipid substrate specificity :
- Class I: Catalyzes the conversion of phosphatidylinositol (4,5)-bisphosphate into phosphatidylinositol (3,4,5)-trisphosphate in vivo .
- Class II: Involved in membrane trafficking and cellular signaling .
- Class III: Plays a role in autophagy and endosomal trafficking .
- Class IV: Less well-characterized but involved in various cellular processes .
PI3Ks are heterodimeric molecules composed of a regulatory and a catalytic subunit . They are expressed in nearly all eukaryotic cells and are involved in key biological processes . The expression patterns and tissue distribution of PI3Ks vary among the different classes and isoforms . For example, Class I PI3Ks are activated by G protein-coupled receptors and tyrosine kinase receptors . PI3Ks are spatially regulated and multifunctional, acting at nearly all membranes in the cell to regulate a wide range of signaling, membrane trafficking, and metabolic processes .
PI3Ks play crucial roles in cell signaling pathways that regulate cell growth, division, migration, and survival . They are central modulators of different cellular signaling pathways and are involved in immune responses and pathogen recognition . For instance, PI3Kγ, a member of Class IB PI3Ks, is involved in the G-protein-dependent regulation of cell signaling in health and disease . PI3Ks also play a role in the activation of various immune cells .
PI3Ks interact with other molecules and cells through various mechanisms . They are activated by cell surface receptors such as G protein-coupled receptors and tyrosine kinase receptors . Upon activation, PI3Ks phosphorylate phosphatidylinositol lipids, leading to the production of phosphatidylinositol (3,4,5)-trisphosphate . This, in turn, recruits downstream signaling proteins with pleckstrin homology domains, such as Akt, to the cell membrane, initiating a cascade of intracellular signaling events . PI3Ks also interact with binding partners such as the p85 regulatory subunit, which stabilizes the catalytic p110 subunit in an inhibited state .
The expression and activity of PI3Ks are tightly regulated through various mechanisms . Transcriptional regulation involves the control of PI3K gene expression by transcription factors . Post-translational modifications, such as phosphorylation and ubiquitination, also play a role in regulating PI3K activity . Non-coding RNAs, such as microRNAs and long non-coding RNAs, are crucial regulators of PI3K gene expression and are involved in the regulation of the PI3K/Akt/mTOR pathway .
PI3Ks have significant applications in biomedical research, diagnostic tools, and therapeutic strategies . In cancer therapy, PI3K inhibitors are used to target the PI3K/Akt/mTOR signaling pathway, which is often dysregulated in cancer . PI3K inhibitors are subdivided into dual PI3K/mTOR inhibitors, pan-PI3K inhibitors, and isoform-specific inhibitors . These inhibitors have shown promising results in clinical trials and are effective in inhibiting tumor progression . PI3Ks are also involved in the treatment of respiratory diseases, such as chronic obstructive pulmonary disease and asthma, by regulating inflammatory responses in the lung .
PI3Ks play a vital role throughout the life cycle, from development to aging and disease . During development, PI3Ks are involved in cell growth, differentiation, and survival . In adulthood, they regulate various physiological processes, including metabolism and immune responses . Dysregulation of PI3K signaling is associated with aging and age-related diseases, such as cancer and neurodegenerative disorders . PI3Ks also play a role in the progression and regression of atherosclerosis by regulating monocyte chemotaxis, macrophage migration, and intracellular lipid accumulation .
