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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Egfr Signaling From The Early Endosome., Julie A. Gosney Aug 2018

Egfr Signaling From The Early Endosome., Julie A. Gosney

Electronic Theses and Dissertations

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is an integral component of proliferative signaling. When activated by a ligand at the plasma membrane, EGFR dimerizes with another ErbB family receptor, leading to kinase domain activation and transphosphorylation of C-terminus tyrosine residues. These phosphotyrosines act as crucial regulators of EGFR signaling as effector proteins dock to the receptor at these sites. The receptor undergoes clathrin-mediated endocytosis into early endosomes, where it can then be trafficked to a lysosome for degradation. However, the kinase domain of EGFR retains its activity during trafficking, suggesting that EGFR can continue ...


Characterization Of Numb As A Regulator Of Anaplastic Lymphoma Kinase, Ran Wei Jun 2016

Characterization Of Numb As A Regulator Of Anaplastic Lymphoma Kinase, Ran Wei

Electronic Thesis and Dissertation Repository

Cellular events rely on protein-protein interactions that are often mediated by modular domains which recognize particular sequence motifs in binding partners. The NUMB protein is the first described cell fate determinant and multifaceted adaptor that is involved in a wide variety of cellular events. NUMB mainly mediates protein interactions via its modular PTB domain. Here we present a systematic investigation of the NUMB-PTB interactome by employing an integrative strategy combining both protein and peptide arrays. We profiled NUMB-PTB binding specificity and interacting proteins genome-wide. The receptor tyrosine kinases (RTKs) are found highly enriched in the interactome, raising the possibility that ...


Requirements Of Rab5 Activity In Highly Invasive Breast Cancer Cell Lines, Nicole Porther, M Alejandro Barbieri Dec 2013

Requirements Of Rab5 Activity In Highly Invasive Breast Cancer Cell Lines, Nicole Porther, M Alejandro Barbieri

Nicole Porther

Rab5 expression in cancer has been associated with the disease progression and prognosis. We have previously shown that growth factor-directed cell invasion and migration was dependent on Rab5 activation in non-invasive breast cancer cells. However, hardly any data is available regarding the role of Rab5 in invasive cells in the presence of growth factor.  In our present study, we report that the invasive and migratory properties of the highly invasive breast cancer cell line, MDAMB-231, were abrogated in cells expressing the inactive (GDP-bound) form of Rab5 irrespective of growth factor stimulation; while the invasive potential of breast cancer cell lines ...


The Role Of Receptor Tyrosine Kinase Axl In Pancreatic Ductal Adenocarcinoma And Its Regulation By Hematopoietic Progenitor Kinase 1, Xianzhou Song Dec 2011

The Role Of Receptor Tyrosine Kinase Axl In Pancreatic Ductal Adenocarcinoma And Its Regulation By Hematopoietic Progenitor Kinase 1, Xianzhou Song

UT GSBS Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies with less than 5% of five year survival rate. New molecular markers and new therapeutic targets are urgently needed for patients with PDA. Oncogenic receptor tyrosine kinase Axl has been reported to be overexpressed in many types of human malignancies, including diffuse glioma, melanoma, osteosarcoma, and carcinomas of lung, colon, prostate, breast, ovary, esophagus, stomach, and kidney. However, the expression and functions of Axl in PDA are unclear. We hypothesized that Axl contributes to the development and progression of PDA. We examined Axl expression in 54 human PDA samples ...


Mechanisms Of The Downregulation Of Prolactin Receptor And Their Role In Cell Proliferation, Bentley J. Varghese May 2010

Mechanisms Of The Downregulation Of Prolactin Receptor And Their Role In Cell Proliferation, Bentley J. Varghese

Publicly Accessible Penn Dissertations

Cells react to diverse stimuli by expressing specific receptors that recognize these stimuli and initiate specific signaling pathways that enable a cell to change with the environment. Downregulation of these signaling receptors represents the most direct method for limiting the magnitude and duration of downstream signal transduction. For cell surface transmembrane receptors, ligand-stimulated endocytosis is a major mechanism by which the ability of a cell to react to a ligand is restricted. In order to investigate the downregulation of the prolactin receptor (PRLr), we investigated the mechanism and key determinants in the endocytosis and downregulation of PRLr. In Chapter 2 ...