PI3Ka Bovine

Phosphoinositide 3-kinase alpha p110a/p85a Bovine Recombinant
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Description

Apoptosis and Cancer Research

PI3Kα Bovine is implicated in apoptosis regulation. Neutralizing antibodies targeting PI3Kα induce caspase-dependent apoptosis in adenocarcinoma cells, reversible by caspase inhibitors . This aligns with studies showing oncogenic PIK3CA mutations drive tumorigenesis via hyperactivation of PI3K/AKT/mTOR pathways .

Keratinocyte Differentiation

PI3Kα activity is essential for keratinocyte adhesion to extracellular matrices. Reduced activity triggers early differentiation phases, highlighting its role in maintaining epidermal integrity .

Adipogenesis Regulation

In bovine adipocytes, PI3Kα interacts with downstream effectors like AKT1 to modulate differentiation. bta-miR-150, which negatively regulates adipogenesis, targets AKT1 in the PI3K/AKT/mTOR pathway . This pathway’s disruption affects lipid deposition, relevant to metabolic studies in cattle .

Kinase Activity Assays

PI3Kα Bovine is used to measure lipid kinase activity in membrane capture assays . Its inhibition by ATP-competitive (e.g., BYL-719) and allosteric compounds provides insights into isoform-specific targeting .

Comparative Insights from Bovine Models

Bovine PI3Kα shares functional homology with human orthologs, making it a viable model for:

  • Signal Transduction Studies: Growth factor responses (insulin, IGF-1) depend on PI3Kα in bovine cells, mirroring human pathways .

  • Metabolic Research: PI3Kα regulates arachidonic acid metabolism, linking oncogenic signaling to dietary fat utilization .

Challenges and Future Directions

While PI3Kα inhibitors like BYL-719 show promise, resistance mechanisms and toxicity remain hurdles . Dual targeting of PI3Kα and mTORC1/2 improves efficacy in glioma stem cells, suggesting combinatorial approaches . Structural studies of bovine PI3Kα could further elucidate isoform-specific drug design .

Product Specs

Introduction
PI3Ka plays a crucial part in the programmed death of human colon cancer cells. When adenocarcinoma cells were treated with antibodies that neutralize PI3Ka, apoptosis was triggered. However, this effect was reversed when the cells were exposed to a caspase inhibitor. Research has also revealed that PI3Ka-mediated phosphorylation of the p85a adapter molecule diminishes the lipid kinase activity within the heterodimer. This finding suggests that PI3K-dependent signaling processes might not always rely on the production of 3'-phosphorylated phosphoinositides. Moreover, PI3Ka is essential for initiating keratinocyte differentiation. Any reduction in PI3Ka activity leads to a decline in keratinocyte adherence to the extracellular matrix, thereby triggering the early stages of differentiation.
Description
The catalytic and regulatory subunits of PI3Ka are simultaneously produced in Sf9 insect cells. This recombinant bovine PI3Ka is a glycosylated protein. Its p85a chain has a molecular weight of 83.5 kDa, while the p110 chain weighs 124.3 kDa.
Physical Appearance
The product is a sterile, filtered liquid.
Formulation
PI3Ka is supplied in a solution containing 25mM HEPES (pH 8.0), 25mM NaCl, 2.5mM MgCl2, and 50% glycerol.
Stability
For optimal storage, keep the product at 4°C if the entire vial will be used within 2-4 weeks. For prolonged storage, freeze at -20°C. Adding a carrier protein (0.1% HSA or BSA) is advised for long-term storage. Avoid repeated freeze-thaw cycles.
Purity
SDS-PAGE analysis indicates a purity exceeding 90%.
Unit Definition
One unit corresponds to the transfer of one picomole of phosphate to PIP2 in one minute.
Specific Activity
The specific activity is 1,000 units per milligram.
Synonyms
Phosphoinositide 3-kinase alpha p110a/p85a, PI3Ka, 2.7.1.137, Phosphatidylinositol 3-kinase, 1-phosphatidylinositol 3-kinase, PI3-kinase, PtdIns-3-kinase, Type I phosphatidylinositol kinase, Type III phosphoinositide 3-kinase.
Source
Sf9 insect cells.

Product Science Overview

Introduction

Phosphoinositide 3-kinases (PI3Ks) are a family of enzymes involved in various cellular functions, including cell growth, proliferation, differentiation, motility, survival, and intracellular trafficking. These enzymes play a crucial role in cellular signaling pathways and are implicated in cancer and other diseases .

Structure and Function

Phosphoinositide 3-kinase alpha (PI3Kα) is a class I PI3K composed of a catalytic subunit (p110α) and a regulatory subunit (p85α). The p110α subunit is encoded by the PIK3CA gene, while the p85α subunit is encoded by the PIK3R1 gene . The catalytic subunit p110α uses ATP to phosphorylate phosphatidylinositols (PtdIns), PtdIns4P, and PtdIns(4,5)P2 .

Role in Cancer

The involvement of p110α in human cancer has been hypothesized since 1995. Genetic and functional studies have shown that common activating PIK3CA missense mutations are present in various human tumors . These mutations are particularly prevalent in breast cancers, with enrichment in the luminal and human epidermal growth factor receptor 2-positive subtypes (HER2+) . The three hotspot mutation positions (GLU542, GLU545, and HIS1047) have been widely reported .

Bovine Recombinant PI3Kα

Phosphoinositide 3-kinase alpha Bovine Recombinant is a glycosylated protein with a molecular weight of approximately 83.5 kDa for the p85α chain and 124.3 kDa for the p110α chain . This recombinant protein is used in various research applications to study the PI3K pathway and its role in cellular signaling and cancer.

Clinical Implications

Due to the association between p110α and cancer, it is considered an appropriate drug target. Pharmaceutical companies are designing and characterizing potential p110α isoform-specific inhibitors . The presence of PIK3CA mutations may also predict the response to certain therapies, such as aspirin therapy for colorectal cancer .

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