erbB3 Is an Active Tyrosine Kinase Capable of Homo- and Heterointeractions

Mara P Steinkamp; Shalini T Low-Nam; Shujie Yang; Keith A Lidke; Diane S Lidke; Bridget S Wilson

doi:10.1128/MCB.01605-13

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erbB3 Is an Active Tyrosine Kinase Capable of Homo- and Heterointeractions

Journal article

Peer reviewed

erbB3 Is an Active Tyrosine Kinase Capable of Homo- and Heterointeractions

Mara P Steinkamp, Shalini T Low-Nam, Shujie Yang, Keith A Lidke, Diane S Lidke and Bridget S Wilson

Molecular and cellular biology, Vol.34(6), pp.965-977

03/15/2014

DOI: 10.1128/MCB.01605-13

PMCID: PMC3958038

PMID: 24379439

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Abstract

ABSTRACT Often considered to be a “dead” kinase, erbB3 is implicated in escape from erbB-targeted cancer therapies. Here, heregulin stimulation is shown to markedly upregulate kinase activity in erbB3 immunoprecipitates. Intact, activated erbB3 phosphorylates tyrosine sites in an exogenous peptide substrate, and this activity is abolished by mutagenesis of lysine 723 in the catalytic domain. Enhanced erbB3 kinase activity is linked to heterointeractions with catalytically active erbB2, since it is largely blocked in cells pretreated with lapatinib or pertuzumab. erbB2 activation of erbB3 is not dependent on equal surface levels of these receptors, since it occurs even in erbB3-transfected CHO cells with disproportionally small amounts of erbB2. We tested a model in which transient erbB3/erbB2 heterointeractions set the stage for erbB3 homodimers to be signaling competent. erbB3 homo- and heterodimerization events were captured in real time on live cells using single-particle tracking of quantum dot probes bound to ligand or hemagglutinin tags on recombinant receptors.

Details

Title: Subtitle: erbB3 Is an Active Tyrosine Kinase Capable of Homo- and Heterointeractions
Creators: Mara P Steinkamp - University of New Mexico Hospital
Shalini T Low-Nam - Department of Pathology, University of New Mexico, Albuquerque, New Mexico, USA
Shujie Yang - University of New Mexico Hospital
Keith A Lidke - University of New Mexico Hospital
Diane S Lidke - University of New Mexico Hospital
Bridget S Wilson - University of New Mexico Hospital
Resource Type: Journal article
Publication Details: Molecular and cellular biology, Vol.34(6), pp.965-977
DOI: 10.1128/MCB.01605-13
PMID: 24379439
PMCID: PMC3958038
NLM abbreviation: Mol Cell Biol
ISSN: 0270-7306
eISSN: 1098-5549
Language: English
Date published: 03/15/2014
Academic Unit: Pathology
Record Identifier: 9984186542802771

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