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Fluctuations in the relative concentrations of proteins in non-stimulated cells can lead to aberrant signaling. In a novel interaction, the SH3 domain of Plcγ1 competes with the SH3 domain of Grb2 for binding to FGFR2 in a concentration-dependent manner. Consequently, reduction of cellular concentrations of Grb2 lead to receptor-dependent recruitment of unphosphorylated Plcγ1. Bringing of the phospholipase to the membrane in this way upregulates its activity, resulting in increased PIP2 turnover to IP3 and DAG resulting in elevated cellular calcium levels. These signaling events increase cell migration and invasion. A further consequence of the depletion of PIP2 is the inhibition of PTEN phosphatase activity. Inhibition of PTEN activity leads to the accumulation of PIP3, which recruits Akt leading to its phosphorylation and activation. Therefore, depletion of Grb2 indirectly leads to activation of the proto-oncogene Akt inducing phenotypic alterations characteristic of tumorigenesis including anchorage-independent cell growth and tumor formation in mice models.
","abstract_html":"<p>@font-face { font-family: "Arial"; }@font-face { font-family: "Calibri"; }p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: Arial; }p.MsoNoSpacing, li.MsoNoSpacing, div.MsoNoSpacing { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: Arial; }div.Section1 { page: Section1; }</p> <p>Fluctuations in the relative concentrations of proteins in non-stimulated cells can lead to aberrant signaling. In a novel interaction, the SH3 domain of Plcγ1 competes with the SH3 domain of Grb2 for binding to FGFR2 in a concentration-dependent manner. Consequently, reduction of cellular concentrations of Grb2 lead to receptor-dependent recruitment of unphosphorylated Plcγ1. Bringing of the phospholipase to the membrane in this way upregulates its activity, resulting in increased PIP<sub>2</sub> turnover to IP<sub>3</sub> and DAG resulting in elevated cellular calcium levels. These signaling events increase cell migration and invasion. A further consequence of the depletion of PIP<sub>2 </sub>is the inhibition of PTEN phosphatase activity. Inhibition of PTEN activity leads to the accumulation of PIP<sub>3</sub>, which recruits Akt leading to its phosphorylation and activation. Therefore, depletion of Grb2 indirectly leads to activation of the proto-oncogene Akt inducing phenotypic alterations characteristic of tumorigenesis including anchorage-independent cell growth and tumor formation in mice models.</p>","abstract_has_math":false,"creators":["timsah, zahra"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["john ladbury","elsa flores","jeffrey frost"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-05-01T07:00:00Z","date_published":"2014-05-01T07:00:00Z","updated_at":"2026-07-24T05:49:23Z","subjects":["Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/422","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["john ladbury","elsa flores","jeffrey frost"]},{"key":"dc:creator","label":"Author","values":["timsah, zahra"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2015-12-31T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation (PhD)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/422"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["@font-face { font-family: \"Arial\"; }@font-face { font-family: \"Calibri\"; }p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: Arial; }p.MsoNoSpacing, li.MsoNoSpacing, div.MsoNoSpacing { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: Arial; }div.Section1 { page: Section1; }
Fluctuations in the relative concentrations of proteins in non-stimulated cells can lead to aberrant signaling. In a novel interaction, the SH3 domain of Plcγ1 competes with the SH3 domain of Grb2 for binding to FGFR2 in a concentration-dependent manner. Consequently, reduction of cellular concentrations of Grb2 lead to receptor-dependent recruitment of unphosphorylated Plcγ1. Bringing of the phospholipase to the membrane in this way upregulates its activity, resulting in increased PIP2 turnover to IP3 and DAG resulting in elevated cellular calcium levels. These signaling events increase cell migration and invasion. A further consequence of the depletion of PIP2 is the inhibition of PTEN phosphatase activity. Inhibition of PTEN activity leads to the accumulation of PIP3, which recruits Akt leading to its phosphorylation and activation. Therefore, depletion of Grb2 indirectly leads to activation of the proto-oncogene Akt inducing phenotypic alterations characteristic of tumorigenesis including anchorage-independent cell growth and tumor formation in mice models.
"]},{"key":"dc:title","label":"Title","values":["Competition Between Grb2 and Plcγ1 For Binding to Fgfr2 Regulates Phospholipase and Pten Activity, Leading to Cell Invasion and Proliferation"]}]}],"canonical_facts":{"dc:contributor":["john ladbury","elsa flores","jeffrey frost"],"dc:creator":["timsah, zahra"],"dc:date.available":["2015-12-31T08:00:00Z"],"dc:description.abstract":["@font-face { font-family: \"Arial\"; }@font-face { font-family: \"Calibri\"; }p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: Arial; }p.MsoNoSpacing, li.MsoNoSpacing, div.MsoNoSpacing { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: Arial; }div.Section1 { page: Section1; }
Fluctuations in the relative concentrations of proteins in non-stimulated cells can lead to aberrant signaling. In a novel interaction, the SH3 domain of Plcγ1 competes with the SH3 domain of Grb2 for binding to FGFR2 in a concentration-dependent manner. Consequently, reduction of cellular concentrations of Grb2 lead to receptor-dependent recruitment of unphosphorylated Plcγ1. Bringing of the phospholipase to the membrane in this way upregulates its activity, resulting in increased PIP2 turnover to IP3 and DAG resulting in elevated cellular calcium levels. These signaling events increase cell migration and invasion. A further consequence of the depletion of PIP2 is the inhibition of PTEN phosphatase activity. Inhibition of PTEN activity leads to the accumulation of PIP3, which recruits Akt leading to its phosphorylation and activation. Therefore, depletion of Grb2 indirectly leads to activation of the proto-oncogene Akt inducing phenotypic alterations characteristic of tumorigenesis including anchorage-independent cell growth and tumor formation in mice models.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/422"],"dc:subject":["Medicine and Health Sciences"],"dc:title":["Competition Between Grb2 and Plcγ1 For Binding to Fgfr2 Regulates Phospholipase and Pten Activity, Leading to Cell Invasion and Proliferation"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:49:23Z"}