Investigation of the Role of JAK2 in SOCS1-mediated Granulocyte-macrophage colony-stimulating Factor Receptor Turnover
Year: 2014
Type: dissertation
Abstract: Our lab has recently shown that SOCS1 binds and degrades the granulocyte-colony stimulating factor receptor beta common subunit (GMRBc) in a proteasome-dependent manner. The focus of this project was to determine the role of JAK2 in SOCS1-mediated GMRBc turnover. Results: The binding of SOCS1 to GMRBc was observed in the JAK2-null gamma2A fibrosarcoma cell line. In TF1s, an erythroleukemic cell line that endogenously expresses GMRBc, transient knockdown of JAK2 resulted in the marked stabilization of GMRBc levels by thirty minutes. Using the kinase-dead K882E JAK2 mutant and the Y1007F JAK2 mutant, which abrogates SOCS1-binding as well as JAK2 activation because it is a key phosphorylation site, it was determined that the kinase activity of JAK2 is required SOCS1-mediated degradation of GMRBc. Lastly, SOCS1 has been predicted to bind Y468 on GMRBc.Conclusions: JAK2 is not necessary for SOCS1 to bind GMRBc; however, active JAK2 is necessary for substantial GMRBc degradation.
Source: TSpace (University of Toronto)
Author: Kamya Kommaraju
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2736093562