Study on signal transduction of chicken proto-oncogene c-ros.
Item
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Title
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Study on signal transduction of chicken proto-oncogene c-ros.
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Identifier
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AAI9605685
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identifier
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9605685
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Creator
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Xiong, Qinghua.
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Contributor
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Adviser: Lu-Hai Wang
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Date
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1995
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Biology, Cell
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Abstract
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Two chimeric receptors, ER1 and ER2, were constructed. ER1 has the extracellular (EC) and transmembrane (TM) domains from EGFR and the cytoplasmic domain from c-ros, whereas ER2 is identical to ER1 except for its TM domain derived form c-ros. Both chimeras promote colony formation with almost equal efficiency. Surprisingly, ER1 inhibits cell growth, while ER2 stimulates it. Flow cytometry analysis reveals that all phases of the cell cycle in ER1 cells are elongated in response to EGF treatment whereas the G1 phase is greatly shortened in ER2 cells.;Comparison of the signaling pathways triggered by the two chimeras reveals several differences: Several early signaling proteins are activated or phosphorylated to higher extent in ER1 cells in response to EGF; ER1 is less efficiently internalized and remains tyrosine phosphorylated for a longer time than ER2; However, phosphorylation of the 66 kD Shc, activation of MAPK and induction of c-fos and c-jun are either to a less extent or for a shorter time in ER1 cells; Cellular protein phosphorylation patterns are also different in ER1 and ER2 cells in response to EGF.;These observations suggest that over-stimulation of ER1, due to its higher EGF binding and retarded internalization, apparently triggers a inhibitory response which counteracts the over-stimulated receptor resulting in growth inhibition.;I also tried to express chicken c-ros, its variants, and v-ros in different cells. The stable lines expressing c-ros and its kinase inactive mutant can not be established in any cell lines. The c-ros variant, ppros, that has a large EC domain deletion can be expressed in MDCK and CV-1 cells. The ppros and ppros-slt which has a three amino acids insertion in the TM domain of ppros can be expressed in CEF at low levels but not transforming. The v-ros can be expressed in NIH3T3 cells and is weakly transforming.;As an independent study, I and members of this lab cloned the chicken PTPase {dollar}\gamma{dollar} cDNA, which is 86.7% identical to human PTPase {dollar}\gamma{dollar} at the amino acid level. PTPase {dollar}\gamma{dollar} could be expressed as an enzymatically active form, but no detectable effects on cell growth and transformation were observed.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
