Cytokine sensitivity and N-glycan processing mutations.
The EGF and TGF-beta families of cytokines are critical regulators of cell proliferation, morphogenesis, and tissue repair. The signaling pathways downstream of EGF and TGF-beta receptors also contribute to cancer growth and metastasis. Cytokine receptors are glycoproteins, and we have recently shown that GlcNAc-branching of N-glycans enhances their cell surface residency and contributes to the growth autonomy of cancer cells. Ligand-induced dimerization of EGF receptors leads to phosphorylation of Erk1/2, whereas TGF-beta binding to its receptors stimulates phosphorylation of Smad2/3. Activated Erk1/2 and Smad2/3 translocate independently into the nucleus and regulate gene expression. Here we describe a sensitive and robust method to quantify TGF-beta and EGF signaling in cancer cells and primary cells from mice by quantitative fluorescence imaging.
Partridge
Emily A
EA
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
Cheung
Pam
P
Dennis
James W
JW
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D006031:Glycosylation; D051379:Mice; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*
D016207:Cytokines; D011134:Polysaccharides