Development of mass spectrometry based technologies for quantitative cell signaling phosphoproteomics : the epidermal growth factor receptor family as a model system

Ligand binding to cell surface receptors initiates a cascade of signaling events regulated by dynamic phosphorylation on a multitude of pathway proteins. Quantitative features, including intensity, timing, and duration of phosphorylation of particular residues play a role in determining cellular response. Mass spectrometry has been previously used to identify and catalog phosphorylation sites or quantify the phosphorylation dynamics of proteins in cell signaling networks. However, identification of phosphorylation sites presents little insight on cellular processes and quantification of phosphorylation dynamics of whole proteins masks the different roles that several phosphorylation sites within one protein have in the network. We have designed a mass spectrometry technique allowing site-specific quantification of dynamic phosphorylation in the cell. We have applied this technique to study signaling events triggered by different members of the epidermal growth factor receptor (EGFR) family. Self organizing maps (SOMs) analysis of our data has highlighted potential biological functions for phosphorylation sites previously unrelated to EGFR signaling and identified network modules regulated by different combinations of EGFR family members. Partial least square regression (PLSR) analysis of our data identified combination of signals strongly correlating with cellular proliferation and migration.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Wolf Yadlin, Alejandro

Advisor dc:contributor.advisor

• Forest M. White.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/38612
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/38612

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/38612