Chan, P. M., Nestler, H. P., Miller, W. T. (November 2000) Investigating the substrate specificity of the HER2/Neu tyrosine kinase using peptide libraries. Cancer Letters, 160 (2). pp. 159-169. ISSN 0304-3835
Abstract
The product of the HER2/Neu oncogene is a receptor tyrosine kinase that is amplified in 25-30% of human primary breast tumors. In this project? we have isolated the HER2/Neu kinase from Sf9 cells infected with a baculovirus expression vector. We probed the substrate specificity of the HER2/Neu kinase using two peptide libraries: (1) a soluble peptide library containing three degenerate positions N-terminal to tyrosine; and (2) a bead-supported combinatorial library possessing sis degenerate positions at P - 1, P - 2, P - 3, P + 1, P + 2, and P + 3. We identified four novel substrate sequences for HER2/Neu from the two peptide libraries. We synthesized these peptides as individual sequences and measured steady-state kinetic properties for phosphorylation by HER2/Neu. One of the peptides, AAEEIYAARRG, is the best synthetic peptide substrate reported to date for HER2/Neu. All of the sequences bear a resemblance to sites of autophosphorylation on HER2/Neu and related epidermal growth factor (EGF) receptor family tyrosine kinases.
Item Type: | Paper |
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Uncontrolled Keywords: | HER2/Neu tyrosine kinase peptide library substrate specificity RETINOBLASTOMA GENE-PRODUCT HUMAN-BREAST-CANCER NEU-ONCOGENE AUTOPHOSPHORYLATION SITES PROTEIN-KINASES EGF RECEPTOR IDENTIFICATION GROWTH TRANSFORMATION MOTIFS |
Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > HER2 diseases & disorders > cancer > cancer types > breast cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase |
CSHL Authors: | |
Communities: | CSHL labs |
Depositing User: | Matt Covey |
Date: | November 2000 |
Date Deposited: | 30 Jan 2014 17:01 |
Last Modified: | 30 Jan 2014 17:01 |
Related URLs: | |
URI: | https://repository.cshl.edu/id/eprint/29408 |
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