Supplied as sterile 50 mM Tris-HCl, pH 7.5, 50-300mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25-1.0mM DTT, 0-0.1mM PMSF, 10-25% glycerol Please contact us for any concerns or special requirements. Please refer to the specific buffer information in the hardcopy of datasheet or the lot-specific COA.
Shipping
Enzymes are highly recommended to be shipped at frozen temperature with dry ice. Shipment made at ambient temperature may seriously affect the activity of the ordered products.
Stability & Storage
Store product at –70°C. For optimal storage, aliquot target into smaller quantities after centrifugation and store at recommended temperature. For most favorable performance, avoid repeated handling and multiple freeze/thaw cycles.
Purity
For specific information on a given lot, see related technical data sheet.
Activity
For specific information on a given lot, see related technical data sheet.
Protein Construction
Recombinant human ACK (110-476) was expressed by baculovirus in Sf9 insect cells using an N-terminal GST tag.
Determination of ATP Km for recombinant protein kinases ACK (Cat. No.: A05-11G) using ADP-GloTM Assay. With saturating substrate concentration, the relative luminescence values were plotted against various ATP concentrations. The Michaelis-Menten equation was then used to generate the Km values. (Validation Experiment)
ACK1 (also known as ACK, TNK2, or activated Cdc42 kinase) is a structurally unique non-receptor tyrosine kinase that is expressed in diverse cell types. This downstream effector of CDC42 mediates CDC42-dependent cell migration via phosphorylation of BCAR1. The ACK1 protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. ACK1 integrates signals from plethora of ligand-activated receptor tyrosine kinases (RTKs), for example, MERTK, EGFR, HER2 and PDGFR to initiate intracellular signaling cascades. It binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR. ACK1 transduces extracellular signals to cytosolic and nuclear effectors such as the protein kinase AKT/PKB and androgen receptor (AR), to promote cell survival and growth. ACK1 participates in tumorigenesis, cell survival, and migration. Gene amplification and overexpression of ACK1 were found in many cancer types such as those of the lung and prostate. Recently, four somatic missense mutations of ACK1, which occur in the N-terminal region, the C-lobe of the kinase domain, and the SH3 domain, were identified in cancer tissue samples.
References
Mahajan K, et al. (2010) Shepherding AKT and androgen receptor by Ack1 tyrosine kinase. J Cell Physiol. 224(2): 327-33.
Chua BT, et al. (2010) Somatic mutation in the ACK1 ubiquitin association domain enhances oncogenic signaling through EGFR regulation in renal cancer derived cells. Mol Oncol. 4(4): 323-34.
Prieto-Echage V, et al. (2010) Cancer-associated mutations activate the nonreceptor tyrosine kinase Ack1. J Biol Chem. 285(14): 10605-15.
title: Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants. authors: Bryan D Smith; Michael D Kaufman; ...; Daniel L Flynn journal: Cancer cell date: 2020-02-14 pmid: 31085175 doi: 10.1016/j.ccell.2019.04.006 cited_by_count: 226 techniques: Droplet Countercurrent Chromatography; Enzyme-linked Immunosorbent Assay; Recombinant bioz_score: 90