title: Measurement of downstream kinase activity modulation as indicator of epidermal growth factor receptor inhibitor efficacy.
abstract: The acoustic membrane micro particle (AMMP) technology has been used to quantify single analytes out of multiple sample types. In this study the technology is used to reveal molecular interactions of components of kinase pathways. Specifically, the downstream kinase activity of the EGFR receptor in the presence or absence of EGFR inhibitors is investigated. These experiments substantiate that EGFR stimulation predominantly activates the MEK/ERK pathway. The EGFR inhibitors tested had varying effectiveness at preventing phosphorylation at the EGFR or downstream kinase activity. These experiments reveal the use of the AMMP technology for observing multiple signaling pathways in a single experiment.
authors: BioScale, Inc., 4 Maguire Road, Lexington, MA 02421, USA. Electronic address: mdickerson@bioscale.com.
authors: W Matthew
authors: WM
authors: Dickerson
authors: BioScale, Inc., 4 Maguire Road, Lexington, MA 02421, USA.
authors: Ashley
authors: A
authors: Saab
authors: BioScale, Inc., 4 Maguire Road, Lexington, MA 02421, USA.
authors: Kristen
authors: K
authors: Leong
authors: BioScale, Inc., 4 Maguire Road, Lexington, MA 02421, USA.
authors: Michael
authors: M
authors: Miller
authors: BioScale, Inc., 4 Maguire Road, Lexington, MA 02421, USA.
authors: Martin
authors: M
authors: Latterich
authors: BioScale, Inc., 4 Maguire Road, Lexington, MA 02421, USA.
authors: Lee Anne
authors: LA
authors: Beausang
authors: BioScale, Inc., 4 Maguire Road, Lexington, MA 02421, USA; Immunologic Consulting, 20 Cahill Park Drive, Framingham, MA 01702, USA.
authors: Edward M
authors: EM
authors: Alderman
mesh_terms: D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D061986:MCF-7 Cells; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D047428:Protein Kinase Inhibitors; D011804:Quinolines; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; C487932:neratinib
keywords: Epidermal growth factor receptor; Intracellular signaling; Pharmacodynamics; Preclinical biomarker analysis; Tyrosine kinase inhibitor