Akt/mTOR/S6K Pathway Explorer Antibody MiniPack

Catalog number: 15-104
Brand: Merck (Millipore)
Packing: 3 vials
Price: € 281.00
Expected delivery time: 7 days
Quantity:

Product specifications for - Akt/mTOR/S6K Pathway Explorer Antibody MiniPack

Overview: 
Product group: Antibodies
Category: Antibody pairs, sets and duo's
Target: AKT1
Target description: v-akt murine thymoma viral oncogene homolog 1
Isotype: IgG1
Properties: 
  Research Use Only
UNSPSC: 12352203
Scientific information: 
Scientific info: Pathway Explorer Antibody MiniPack:Each Pathway Explorer Antibody Minipack contains three related antibodies as part of a signaling cascade or a combination of total and phosphorylated forms of key signaling targets. Each of the three antibodies are 30% the original pack size. Full size versions of each of the Pathway Explorer antibodies are available for sale individually under the same catalog number with the removal of “SP” off of each one (e.g. 05-591SP can be ordered as 05-591). Akt:Akt (Protein Kinase B), a Ser/Thr kinase, is a major known effecter of the PI3 Kinase pathway and is involved in multiple signaling pathways that relate to many biological processes including glucose metabolism, cell survival/apoptosis, cell cycle control, angiogenesis, differentiation, and cell growth and proliferation. Akt is activated by ligand-stimulated growth factor receptor signaling that activates the Phosphatidylinositol 3-kinase (PI3 Kinase, PI3K) dependent manner. PKB is one of the most frequently hyperactivated protein kinases in human cancers. In mammals three isoforms of Akt (Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma) exists. They exhibit a high degree of homology, but differ slightly in the localization of their regulatory phosphorylation sites. Akt1 is the predominant isoform that is in most tissues and is thought to have a dominant role in growth, survival, embryonic development, and post-natal survival. Additionally, Akt1/PKBalpha is required for adipocyte differentiation, where as Akt2/PKBbeta and Akt3/PKBgamma are not. Akt2 is strongly correlated with the regulation of glucose homeostasis and is the predominant PKB isoform expressed in insulin-responsive tissues where defective Akt2 results in impaired insulin-stimulated glucose uptake in muscle and adipocytes. Akt gamma is abundant in brain tissue. Each Akt isoform is composed of three functionally distinct regions: an N-terminal Pleckstrin Homology (PH) domain that provides a lipid-binding module to direct Akt to PIP3 at the cell membrane as a result of PI3 Kinase (PI3K) activity that is necessary for its activation, a central catalytic domain, and a C-terminal hydrophobic motif. The activation and regulation of AKT is dependent on a dual regulatory mechanism that requires both its translocation to the plasma membrane and dual phosphorylation on Thr308 and Ser473 by PDK1 and the TORC2 complex, respectively. This is accomplished by the generation and build-up of PIP3 by PI3K in conjunction with reduced PTEN function that results in the activation of PDK1 (3-phosphoinositide-dependent protein kinase-1) and the recruitment of AKT to the plasma membrane by direct interaction with its PH domain. The activated PDK1 then in turn phosphorylates Akt on Thr308 in its activation loop. This phosphorylation is necessary and sufficient for AKT activation, however maximal activation requires the additional phosphorylation at Ser473. Another kinase complex, recently identified as TORC2, which is composed of the mTOR, Rictor, GbetaL, Sin1, and Protor1 and 2 (previously referred to as the unidentified kinase PDK2), phosphorylates AKT on Ser473 in its hydrophobic motif. After Akt is activated, it is liberated from the plasma membrane and released into the cytosol and nucleus where it interacts with and phosphorylates multiple binding partners. It has been shown to phosphorylate over 40 substrates, some of which are activated by phosphorylation such as mTOR, AS160, PRAS40 (Thr246), IKK, MDM2, NFkappaB, and TSC1&2 and some that are inhibited by its phosphorylation that include Bad (Ser136), GSK3 (Ser9), FKHR (Ser256), and Caspase 9 (Ser196). Just as these two AKT phosphorylation sites are phosphorylated by two separate mechanisms, they are both regulated by two different phosphatases. The dephosphorylation and subsequent inactivation of AKT is much less understood than its activation. It was not until the recent discovery of two new phosphatases, PHLPP1 and PHLPP2 (PH domain leucine-rich repeat protein phosphatase) that the process was better elucidated. Dephosphorylation of AKT at Ser473, but not at Thr308, was found to be mediated by one or both of the PHLPP family of phosphatases. Another more promiscuous phosphatase, PP2A, is now believed to dephosphorylate AKT on the PDK1 phosphorylation site at Thr308. Together these phosphatases help regulate the activity of AKT. With AKT having so many signaling partners and its involvement in multiple signaling pathways and cellular mechanisms, it is no wonder why AKT is so well studied and a highly sought after drug target.mTOR:mTOR (Mammalian Target of Rapamycin, aka FRAP, RAPT or RAFT) is a large 289 kDa Ser/Thr protein kinase that regulates cell cycle progression, cell growth, protein synthesis, ribosome biogenesis, and autophagy. mTOR is an evolutionarily conserved member of the Phosphoinositol Kinase-related Kinase (PIKK) family whose activity is regulated by phosphorylation on Ser2448 by Akt in response to insulin or muscle activity. Interestingly, mTOR is the central component of two multimeric kinase complexes consisting of mTOR and numerous other mTOR binding proteins. These two multimeric protein complexes are designated mTORC1 and mTORC2. mTORC1 (mTOR Complex 1) consists of at least mTOR, Raptor, and GbetaL (mLST8). mTORC1 is known to play a central role in insulin signaling, which is crucial in maintaining metabolic homeostasis. The complex is activated primarily though the PI3 Kinase/Akt pathway. Upon insulin stimulation, Akt activates mTORC1 by phosphorylating and inhibiting TSC (and possibly other yet discovered targets and/or mTOR itself). This inhibits the upstream small GTPase regulator Rheb (Ras homolog enriched in brain). This inhibits the kinase activity of the mTORC1 complex, thus disabling its ability to phosphorylate its downstream targets such as p70 S6K on Thr389 and 4E-BP1 on Thr229. The other mTOR complex, mTORC2 (mTOR Complex 2), is made up of at least mTOR, Rictor, G?L, Sin1, Protor 1 and 2. mTORC2 affects cell proliferation and survival primarily by phosphorylating the hydrophobic motif of Akt on Ser473, a well-known effecter of the PI3 Kinase pathway. In addition to phosphorylating Akt, the mTORC2 complex is also known to effect cytoskeletal organization and migration by exerting its effects through Rac, Rho, and PKC. Interestingly, unlike mTORC1, the mTORC2 complex appears to not be inhibited by treatment with rapamycin and for this reason is referred to as the rapamycin-insensitive complex. Defects in both mTOR complexes are associated with a variety of diseases, including cancer and diabetes.p70 S6K:S6 Kinase is a Ser/Thr kinase which phosphorylates the 40S ribosomal protein S6, and several translation-regulatory factors. S6 kinase is activated by phosphorylation of multiple sites by mTOR. S6K is an important regulator of protein synthesis, along with MAP Kinase. In neurons, S6K is linked to the cytoskeleton by neurabin, which may play a role in its activation. Rsk3 (MAPKAP Kinase 1c) and Rsk4 are also known as the Ribosomal Protein S6 Kinase, 90 kDa, polypeptide 2 and 6, respectively.See full size versions for corresponding references.
Gene ID: 207
Additional information: 
Synonyms: 15-104; Merck; Millipore