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A novel adaptor-like protein which is a substrate for the non-receptor tyrosine kinase, BRK

Oncogene volume 19, pages 4273–4282 (2000)Cite this article

Abstract

The brk gene encodes a non-receptor tyrosine kinase that has been found to be overexpressed in approximately two thirds of breast tumours. Using a yeast two-hybrid based screen, we have cloned cDNAs encoding a novel protein, BKS, that is a substrate for the kinase activity of BRK and has the characteristics of an adaptor protein. BKS possesses an N-terminal PH-like domain followed by an SH2-like domain. In co-transfection experiments, high levels of phosphotyrosine were observed on BKS and BRK was found to be associated with BKS, both of which were dependent on the catalytic activity of BRK. The phosphorylation of and association with BKS by BRK was also dependent on the SH2-like domain present within BKS. In addition, BKS recruited an unidentified 100 kDa protein that was also phosphorylated on tyrosine residues in the presence of BRK. We have determined that the BKS protein is expressed in most adult human tissues.

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Acknowledgements

We would like to thank Robin Brown (Glaxo-Wellcome, Stevenage, UK) for the yeast two-hybrid bait vector. pYTH6, the yeast strain, Y190, and for all his helpful advice. We are indebted to Daphne Hughes and Barry Gusterson for the collection of normal human tissues. We thank Carolanne Brown for running the Jean Rook automated sequencing facility, which is funded by BREAKTHROUGH breast cancer, Karen Barker for the breast tumour cell line protein lysates and Paul Smith and Mike Fry for the helpful discussions. This work was funded by research grants from the Wellcome Foundation (PJ Mitchell & MR Crompton) and the Cancer Research Campaign (EA Sara).

These sequence data have been submitted to the DDBJ/EMBL/GenBank databases under accession number: AJ245719

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  1. Philip J Mitchell

    Present address: MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK

Authors and Affiliations

  1. Section of Cell Biology and Experimental Pathology, The Breakthrough Toby Robinson Cancer Research Centre, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK

    Philip J Mitchell, Elizabeth A Sara & Mark R Crompton

  2. School of Biological Sciences, Royal Hollaway, University of London, Egham, TW20 0EX, Surrey, UK

    Mark R Crompton

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Mitchell, P., Sara, E. & Crompton, M. A novel adaptor-like protein which is a substrate for the non-receptor tyrosine kinase, BRK. Oncogene 19, 4273–4282 (2000). https://doi.org/10.1038/sj.onc.1203775

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