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Investigating the role of protein tyrosine phosphatase alpha in focal adhesion dynamics and cell migration

University of British Columbia

Cell migration is an important phenomenon in many physiological and pathological processes such as wound healing, embryogenesis, and cancer cell metastasis. Integrins bind components of the extracellular matrix and initiate a cascade of intracellular signaling changes that regulate focal adhesion dynamics and reorganization of the actin cytoskeleton. Focal adhesions are multiprotein complexes that are continuously assembled, remodeled, and disassembled to enable cell migration. Protein tyrosine phosphatase alpha (PTPα) is a receptor-like transmembrane protein that is involved in integrin signaling. In response to integrin stimulation, PTPα mediates Src activation through dephosphorylation of the inhibitory phosphosite of Src. This leads to formation of the Src-FAK complex which in turn phosphorylates PTPα at the Tyr789 site. PTPα-Tyr789 phosphorylation has been demonstrated to be an important event in coordinating focal adhesion formation, cytoskeletal rearrangement, and cell migration. Mouse embryonic fibroblasts (MEFs) lacking PTPα expression or expressing an unphosphorylatable mutant (Y789F) PTPα exhibit impaired focal adhesion formation and cell migration. In this study, I investigated the focal adhesion dynamics and cell migration capabilities of newly generated lines of wild-type and PTPα-deficient MEFs. Although these newly generated cells did not fully recapitulate the previously reported PTPα-dependent focal adhesion dynamics and cell migration defects, I observed that cells lacking PTPα expression exhibited defects in cell polarity and directionality, mechanisms that coordinate migration. My findings suggest that alterations to key signaling components or pathways in these cells may be responsible for coordinating focal adhesion dynamics and cell migration irrespective of PTPα expression.

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2017-07-04

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/62137

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/