Biological & Disease Relevance

Newest kinase targets and their disease relevance:

mTOR
The mammalian target of rapamycin (mTOR, a.k.a. FRAP, RAFT) is a member of the phosphoinositol kinase-related kinase (PIKK) family of serine/threonine protein kinases. mTOR plays a key role in cell growth and homeostasis and may be abnormally regulated in tumors. Recent studies have linked mTOR to several human diseases including cancer, diabetes, obesity, cardiovascular and age-related diseases and neurological disorders.

Plk1
Polo-like kinase-1 (Plk1) is a member of the Plk family of serine/threonine kinases. It is an important regulator of several events during mitosis and recent studies have suggested that Plk1 is involved in both G2 and mitotic DNA damage checkpoints. Overexpression of Plk1 has been detected in a variety of cancers, and expression levels often correlate with poor prognosis.

PI3Kα/p85α, PI3Kβ/p85β
Phosphatidylinositol 3-kinaseα /p85α (PI3Kα/p85α) and phosphatidylinositol 3-kinaseβ/p85β (PI3Kβ/p85β) are members of a family of class I phosphatidylinositol 3-kinase (PI3K) enzymes that phosphorylate phosphoinositides at the 3-hydroxyl of the inositol ring. These enzymes play key roles in a diverse range of cellular processes including proliferation, survival, metabolism, adhesion and cell motility. A number of point mutations, including E542K, E545K & H1047R, within the catalytic subunit of PI3Kα have been associated with tumours of the colon, stomach, breast and brain. Combined in vitro and in vivo studies have shown that these mutations confer higher lipid kinase activity than wild type, and are able to induce oncogenic transformation.

A truncated variant of the p85α regulator, p65α, has also been associated with cancer. This subunit has been shown to bind but not inhibit p110, leading to constitutive PI3K activity.

mTOR/FKBP12
The mammalian target of rapamycin (mTOR) is an important protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. Current research indicates that mTOR integrates the input from multiple upstream pathways, including insulin, growth factors and mitogens. mTOR also functions as a sensor of cellular nutrient/energy levels and redox status. The dysregulation of the mTOR pathway is implicated as a contributing factor to a number of human diseases including various types of cancer.

FKBP12 is a 12kDa immunophilin that binds immunosuppressant drugs such as FK-506 (tacrolimus) and rapamycin (sirolimus). The FKBP12-rapamycin complex is able to interact with mTOR resulting in inhibition of its kinase activity. In the absence of FKBP12, mTOR is insensitive to rapamycin.

PI3Kα(E542K)/p85α (m), PI3Kβ/p85α (m), PI3Kδ/p85α (m)
Phosphatidylinositol 3-kinaseα/p85α (PI3Kα/p85α), phosphatidylinositol 3-kinaseβ/p85α (PI3Kβ/p85α) and phosphatidylinositol 3-kinaseδ/p85α (PI3Kδ/p85α) are members of a family of class I phosphatidylinositol 3-kinase (PI3K) enzymes that phosphorylate phosphoinositides at the 3-hydroxyl of the inositol ring. These enzymes play key roles in a diverse range of cellular processes including proliferation, survival, metabolism, adhesion and cell motility. A number of point mutations, including E542K, E545K & H1047R, within the catalytic subunit of PI3Kα have been associated with tumours of the colon, stomach, breast and brain. Combined in vitro and in vivo studies have shown that these mutations confer higher lipid kinase activity than wild type, and are able to induce oncogenic transformation.

Tec
Tyrosine kinase expressed in hepatocellular carcinoma (Tec) is the prototypical member of the Tec tyrosine kinase family. These enzymes (Tec, Btk, Itk, Bmx, and Txk) are involved in the intracellular signaling mechanisms of cytokine receptors, lymphocyte surface antigens, heterotrimeric G-protein coupled receptors, and integrin molecules. They are also key players in the regulation of the immune functions. Tec is an integral component of T cell signaling and has a distinct role in T cell activation leading to IL-2 production.

Please note, mTOR/FKBP12 (catalogue no. 14-769FK) is released to KP ONLY.