N-glycans of growth factor receptors: their role in receptor function and disease implications

2016 ◽  
Vol 130 (20) ◽  
pp. 1781-1792 ◽  
Author(s):  
Motoko Takahashi ◽  
Yoshihiro Hasegawa ◽  
Congxiao Gao ◽  
Yoshio Kuroki ◽  
Naoyuki Taniguchi
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Cell Signalling ◽  
Growth Factor Receptor ◽  
Transforming Growth Factor Β ◽  
Cellular Events ◽  
Functional Regulation ◽  
Epidermal Growth ◽  
Β Receptor ◽  
Novel Strategy

Numerous signal-transduction-related molecules are secreted proteins or membrane proteins, and the mechanism by which these molecules are regulated by glycan chains is a very important issue for developing an understanding of the cellular events that transpire. This review covers the functional regulation of epidermal growth factor receptor (EGFR), ErbB3 and the transforming growth factor β (TGF-β) receptor by N-glycans. This review shows that the N-glycans play important roles in regulating protein conformation and interactions with carbohydrate recognition molecules. These results point to the possibility of a novel strategy for controlling cell signalling and developing novel glycan-based therapeutics.

Stimulation of DNA Synthesis by Interferon and Transforming Growth Factor β in EL2 Rat Fibroblasts. Role of This Effect on the Expression of an EL2-Transformed Phenoptype

1988 ◽  
Vol 1 (3) ◽  
pp. 185-191
Author(s):  
P. Di Francesco ◽  
E. Liboi ◽  
G. Febbraro ◽  
C. Favalli
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Cellular Events ◽  
Growth Inhibitory ◽  
Fibroblast Line ◽  
Epidermal Growth ◽  
Rat Fibroblasts ◽  
Malignant Conversion

The proliferation of normal cells is regulated by both positive and negative growth-effects, induced by growth-stimulatory factors [e.g., Platelet Derived Growth Factor (PDGF), Fibroblast Growth Factor (FGF), Epidermal Growth Factor (EGF)] and growth-inhibitory factors [e.g., Interferons (IFNs), Transforming Growth Factor β (TGFβ), Tumor Necrosis Factor (TNF)]. To investigate these effects, we analyzed DNA synthesis in an euploid fibroblast line (EL2), recently isolated from rat embryo, stimulated with EGF and treated with TGFβ and IFN respectively. Our results show that, in opposition to what is described for other fibroblast lines, in EL2 cells the treatment with appropriate concentrations of TGFβ or IFN did not inhibit the [3H]-thymidine incorporation induced by EGF, but, on the contrary, EGF-induced DNA synthesis was greatly stimulated by the presence of TGFβ or IFN in our cell cultures. The implications of these findings for elucidating the cellular events leading to the malignant conversion are discussed.

scholarly journals Inactivation of Smad-Transforming Growth Factor β Signaling by Ca2+-Calmodulin-Dependent Protein Kinase II

2000 ◽  
Vol 20 (21) ◽  
pp. 8103-8111 ◽  
Author(s):  
Stephen J. Wicks ◽  
Stephen Lui ◽  
Nadia Abdel-Wahab ◽  
Roger M. Mason ◽  
Andrew Chantry
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Transforming Growth Factor Β ◽  
Cam Kinase Ii ◽  
Cam Kinase ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Β Receptor

ABSTRACT Members of the transforming growth factor β (TGF-β) family transduce signals through Smad proteins. Smad signaling can be regulated by the Ras/Erk/mitogen-activated protein pathway in response to receptor tyrosine kinase activation and the gamma interferon pathway and also by the functional interaction of Smad2 with Ca2+-calmodulin. Here we report that Smad–TGF-β-dependent transcriptional responses are prevented by expression of a constitutively activated Ca2+-calmodulin-dependent protein kinase II (Cam kinase II). Smad2 is a target substrate for Cam kinase II in vitro at serine-110, -240, and -260. Cam kinase II induces in vivo phosphorylation of Smad2 and Smad4 and, to a lesser extent, Smad3. A phosphopeptide antiserum raised against Smad2 phosphoserine-240 reacted with Smad2 in vivo when coexpressed with Cam kinase II and by activation of the platelet-derived growth factor receptor, the epidermal growth factor receptor, HER2 (c-erbB2), and the TGF-β receptor. Furthermore, Cam kinase II blocked nuclear accumulation of a Smad2 and induced Smad2-Smad4 hetero-oligomerization independently of TGF-β receptor activation, while preventing TGF-β-dependent Smad2-Smad3 interactions. These findings provide a novel cross-talk mechanism by which Ca2+-dependent kinases activated downstream of multiple growth factor receptors antagonize cell responses to TGF-β.

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