Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases with important roles in signal transduction. PI3Ks are involved in signal propagation for diverse receptors including tyrosine kinase receptors and G-protein coupled receptors. Class I PI3Ks consist of two subunits: the regulatory p85 subunit and the catalytic p110 subunit (1). p85 binds to phosphorylated tyrosine residues found on activated tyrosine kinase receptors and mediates the translocation of the p110 subunit to the cell membrane (2). Once at the cell periphery PI3K phosphorylates the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 acts as a second messenger by recruiting the kinase Akt and facilitating its activation (2). Akt can then activate downstream effectors to regulate diverse cell behaviors including growth, proliferation, and migration. PI3Ks are commonly misregulated in cancers which has led to interest in the development of PI3K inhibitors (2). The p110 subunit exists in four isoforms: alpha, beta, delta, and gamma. While p110 alpha and p110 beta are ubiquitously expressed p110 delta is expressed primarily in white blood cells where it functions in the development of B-cells and T-cells. Specific inhibition of p110 delta may prove to be an effective tool to block the constitutive activation of PI3K in chronic lymphocytic leukemia (1). p110 delta antibodies and p110 delta knockout mice have been excellent tools to study the role of this cell-type specific PI3K component. A group from the Medical College of Wisconsin examined the role p110 delta in natural killer cells by expressing catalytically inactive mutants (3). By using these mutants along with western blotting with the p110 delta antibody the authors were able to demonstrate the importance of p110 delta for natural killer cell maturation and cytokine generation (3). While essential for leukocyte biology, p110 delta has also recently been shown to function rheumatoid arthritis (RA) (4). Researchers from the University of California San Diego used p110 delta antibodies to show increased p110 delta expression in fibroblast-like synoviocytes (4). They also used the p110 delta antibody for immunohistochemistry to visualize expression in the synovial lining (4). This study demonstrates a previously unknown role for p110 delta in the regulation of synoviocyte growth and apoptosis through PI3K signaling. p110 delta antibodies will continue to serve an important function in the future research of isoform specific PI3K heterodimers and their role in various diseases from arthritis to leukemia.
Novus Biologicals offers PI 3-Kinase p110 delta reagents for your research needs including:
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