Promiscuous receptors

Credit: Alfred Pasieka / Photo Researchers, Inc. The paper: R.B. Jones et al., "A quantitative protein interaction network for the ErbB receptors using protein microarrays," Nature, 439:168–74, 2006.

By | March 1, 2008

<figcaption> Credit: Alfred Pasieka / Photo Researchers,
					Inc.</figcaption>
Credit: Alfred Pasieka / Photo Researchers, Inc.

The paper:

R.B. Jones et al., "A quantitative protein interaction network for the ErbB receptors using protein microarrays," Nature, 439:168–74, 2006. (Cited in 98 papers)

The finding:

Gavin MacBeath's team at Harvard University wanted to find the proteins that get recruited to receptors in the first step of epidermal growth factor signaling. Using microarrays to perform a genome-wide assessment of the receptor network, they found that EGFR and ErbB2 bind to proteins more promiscuously, and activate many more signaling pathways, as they are overexpressed.

The link:

This paper enforced previous observations that overexpression of the EGFR and ErbB2 receptors are associated with human cancers; these receptors may turn on different signaling pathways that could alter the state of the cell, in some cases leading to uncontrollable cell division.

The application:

MacBeath said his group has found in follow-up work that their data can predict the differences in downstream signaling that occur with changes in the expression of other receptors (yet unpublished). These measurements can be used to create models of the biologic responses to varying receptor expression, wrote Robert Weinberg of the Whitehead Institute in an E-mail.

The work:

MacBeath's group has expanded its use of microarrays to look beyond ErbB at every phosphotyrosine binding domain in the human genome, examining more downstream signaling events that result from altered receptor expression.

Expression level (KD) Number of proteins binding
EGFR 500 <20
2,000 >40
ErbB2 500 <20
2,000 >60

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