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A genetic approach to identify the requirements for phosphotyrosine specific outputs of Neu/ErbB2

<p> DER, the Drosophila Epidermal Growth Factor Receptor (DEgfr) is
the only known fly orthologue of vertebrate Neu/ErbB2 receptor tyrosine
kinase family. Receptor Tyrosine Kinases (RTKs) like DER and ErbB2 play
an important role in regulating cell differentiation, cell proliferation and cell
survival in metazoan animals. Neu/ErbB2 is over-expressed in 20-30% human
breast cancers, which correlates with poor clinical prognosis in cancer
patients. </p> <p> Our previous studies showed that rat-NeriJErbB2 could successfully
signal in vivo using Drosophila adaptor and second messenger molecules.
Here we regenerated the transgenic fly lines with various neu add-back alleles.
We further re-established mis-expression phenotypes in various adult
structures such as wings and eyes, the tissues known to require DEgfr
signaling. By using genetic approach, we have demonstrated that the tyrosine
residue at the 1028 site (NeuYA), might have an inhibitory role in RTK
signaling. In addition we have already generated a number of double add-back
neu alleles where tyrosine site at the 1028 site (neuYA) was added back to
another Neu allele and made neuYAB, neuYAc neuYAD and neuYAE. Transgenic flies
with these alleles will be generated to further study the inhibitory role of
Neu^YA. </p> <p> Finally, our on going large-scale genetic screening is likely to reveal the
component(s) of NeuYE (Y1253) pathway that does not utilize the function of
Ras. </p> / Thesis / Master of Science (MSc)

Identiferoai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/21652
Date04 1900
CreatorsHossain, Noor
ContributorsJacobs, J., Biology
Source SetsMcMaster University
LanguageEnglish
Detected LanguageEnglish

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