scholarly journals Endocytosis and Transport of Growth Factor Receptors in Peripheral Axon Regeneration: Novel Lessons from Neurons Expressing Lysine‐Deficient FGF Receptor Type 1 in vitro

2019 ◽  
Vol 302 (8) ◽  
pp. 1268-1275 ◽  
Author(s):  
Barbara Hausott ◽  
Alexandra Förste ◽  
Fabian Zach ◽  
Stefan Mangger ◽  
Ellen Margrethe Haugsten ◽  
...  
Keyword(s):  
Growth Factor ◽  
Axon Regeneration ◽  
Growth Factor Receptors ◽  
Receptor Type ◽  
Fgf Receptor ◽  
Peripheral Axon

A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor tyrosine kinase

1994 ◽  
Vol 14 (1) ◽  
pp. 509-517
Author(s):  
W Li ◽  
R Nishimura ◽  
A Kashishian ◽  
A G Batzer ◽  
W J Kim ◽  
...  
Keyword(s):  
Growth Factor ◽  
Intracellular Signaling ◽  
Egf Receptor ◽  
Tyrosine Phosphatase ◽  
Growth Factor Receptors ◽  
Ras Signaling ◽  
Pdgf Receptor ◽  
Phosphotyrosine Phosphatase ◽  
Src Homology

Autophosphorylated growth factor receptors provide binding sites for the src homology 2 domains of intracellular signaling molecules. In response to epidermal growth factor (EGF), the activated EGF receptor binds to a complex containing the signaling protein GRB2 and the Ras guanine nucleotide-releasing factor Sos, leading to activation of the Ras signaling pathway. We have investigated whether the platelet-derived growth factor (PDGF) receptor binds GRB2-Sos. In contrast with the EGF receptor, the GRB2 does not bind to the PDGF receptor directly. Instead, PDGF stimulation induces the formation of a complex containing GRB2; 70-, 80-, and 110-kDa tyrosine-phosphorylated proteins; and the PDGF receptor. Moreover, GRB2 binds directly to the 70-kDa protein but not to the PDGF receptor. Using a panel of PDGF beta-receptor mutants with altered tyrosine phosphorylation sites, we identified Tyr-1009 in the PDGF receptor as required for GRB2 binding. Binding is inhibited by a phosphopeptide containing a YXNX motif. The protein tyrosine phosphatase Syp/PTP1D/SHPTP2/PTP2C is approximately 70 kDa, binds to the PDGF receptor via Tyr-1009, and contains several YXNX sequences. We found that the 70-kDa protein that binds to the PDGF receptor and to GRB2 comigrates with Syp and is recognized by anti-Syp antibodies. Furthermore, both GRB2 and Sos coimmunoprecipitate with Syp from lysates of PDGF-stimulated cells, and GRB2 binds directly to tyrosine-phosphorylated Syp in vitro. These results indicate that GRB2 interacts with different growth factor receptors by different mechanisms and the cytoplasmic phosphotyrosine phosphatase Syp acts as an adapter between the PDGF receptor and the GRB2-Sos complex.

scholarly journals Differential effects of fibroblast growth factor (FGF) 9 and FGF2 on proliferation, differentiation and terminal differentiation of chondrocytic cells in vitro

1999 ◽  
Vol 342 (3) ◽  
pp. 677-682 ◽  
Author(s):  
Nicole B. WEKSLER ◽  
Gregory P. LUNSTRUM ◽  
Eric S. REID ◽  
William A. HORTON
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Physiological Responses ◽  
Terminal Differentiation ◽  
Receptor Activation ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Chondrocytic Differentiation ◽  
Mitotic Inhibitor

Fibroblast growth factor (FGF) 9 was compared with FGF2 in its ability to influence proliferation, differentiation, terminal differentiation and apoptosis in a rat calvaria-derived cell line (RCJ 3.1C5.18) that spontaneously undergoes chondrocyte differentiation in vitro. Like FGF2, FGF9 promoted proliferation, but to a lesser extent. In contrast to FGF2, which blocked chondrocytic differentiation, FGF9 had no effect on differentiation but inhibited terminal differentiation. FGF9 also stimulated expression of the mitotic inhibitor p21 to a greater extent than FGF2. Neither ligand influenced apoptosis. The results indicate that FGF9 could account for many of the physiological responses attributed to FGF-receptor activation in the growth plate.

127 Temporal regulation of molecular pathways, metabolic enzymes and growth factor receptors during bovine oocyte maturation in vitro

2019 ◽  
Vol 31 (1) ◽  
pp. 189
Author(s):  
S. Rajput ◽  
J. Becker ◽  
Y. Yuan ◽  
W. Schoolcraft ◽  
R. Krisher
Keyword(s):  
Growth Factor ◽  
Oocyte Maturation ◽  
Growth Factor Receptors ◽  
Cumulus Cells ◽  
Metabolic Enzymes ◽  
Molecular Pathways ◽  
Temporal Regulation ◽  
Maturation In Vitro ◽  
Significant Change

Although great efforts have been made to improve in vitro oocyte maturation (IVM) medium, we have yet to achieve competence equivalent to in vivo-matured oocytes. The failure in development of culture conditions for IVM yielding high quality eggs is attributed to an incomplete understanding of molecular pathways regulating oocyte and cumulus cell metabolism. The objective of the present study was to characterise the expression and functional activity of cell signalling pathways (mTOR, AKT, 4EBP1, ERK1/2), metabolic enzymes (PKM2, PDH, LDHA, AMPK), and growth factor receptors (IGF1R, IGFIIR, EGFR, FGFR1) in bovine oocytes and cumulus cells before and after in vitro maturation. In vitro-derived cumulus-oocyte complexes were collected at germinal vesicle (GV) and metaphase II (MII) stages (20 cumulus-oocyte complexes per stage; n=3 replicates) and subjected separately to Western blot analysis using antibodies against both phosphorylated (p) and total (t) protein abundance; the ratio p:t was used to determine the activity of each pathway. Results demonstrate increased (P<0.05) mTOR and ERK1/2 signalling, with no change in AKT and 4EBP1 activity, in oocytes during IVM. We observed increased (P<0.05) abundance of oocyte t-ERK from the GV to MII stage, but total expression of AKT, mTOR and 4EBP1 did not change. In cumulus cells, there was a significant (P<0.05) reduction in mTOR and 4EBP1, an increase in AKT, and no significant change in ERK activity. Analysis of metabolic enzymes in oocytes demonstrated increased (P<0.05) PDH, reduced AMPK, and unchanged PKM2 and LDHA phosphorylation during IVM. However, increased expression of t-PKM2 abundance was observed from the GV to MII stage. In cumulus cells, tAMPK abundance was reduced (P>0.05), but no significant change was observed in the activity of other metabolic enzymes analysed during IVM. Finally, we observed abundant expression of IGF2R in the oocyte compared with other growth factor receptors analysed, although IGF2R was significantly (P<0.05) reduced from GV to MII oocytes. In cumulus cells, both IGF1R and IGF2R were highly abundant compared with EGFR and FGFR but did not change during IVM. Data were analysed using one-way ANOVA. Results suggest that regulatory mechanisms including AKT/mTOR/4EBP1 and ERK are entirely different in oocytes and cumulus cells during maturation. An increase in the inhibitory phosphorylation of oocyte PDH (S293) toward the end of maturation suggests low metabolism of pyruvate via the Krebs cycle at that time. Similarly, dephosphorylation of AMPK (T172) suggests reduced AMPK activity and reduced fatty acid oxidation in mature oocytes. In addition, temporal regulation of IGF1R in the oocyte and EGFR in cumulus cells suggests an important role for these growth factor receptors during maturation and that these growth factors could be used to improve IVM medium in the bovine. Collectively, these results increase our understanding of the molecular pathways regulating oocyte metabolism during maturation and provide a strategy to improve the IVM environment for assisted reproductive technology.

Heterodimerization of FGF-receptor 1 and PDGF-receptor-α: a novel mechanism underlying the inhibitory effect of PDGF-BB on FGF-2 in human cells

Blood ◽  
2006 ◽  
Vol 107 (5) ◽  
pp. 1896-1902 ◽  
Author(s):  
Debora Faraone ◽  
Maria S. Aguzzi ◽  
Gianluca Ragone ◽  
Katia Russo ◽  
Maurizio C. Capogrossi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Intracellular Signaling ◽  
Cell Function ◽  
Umbilical Vein ◽  
Pdgf Receptor ◽  
Inhibitory Effects ◽  
Fgf Receptor ◽  
Endothelial Cell Function

Previous evidence has shown that platelet-derived growth factor-BB (PDGF-BB) and fibroblast growth factor-2 (FGF-2) directly interact with high affinity, leading to potent reciprocal inhibitory effects on bovine endothelial cells and rat vascular smooth muscle cells. In this study, we report that PDGF-BB inhibits a series of FGF-2–induced events, such as proliferation of human umbilical vein endothelial cells (HUVECs), FGF-2 cellular internalization, phosphorylation of intracellular signaling factors including p38, rac1/cdc42, MKK4, and MKK3/6, and phosphorylation of FGF-receptor 1 (FGF-R1). PDGF-receptor-α (PDGF-Rα) was found to mediate PDGF-BB inhibitory effects because its neutralization fully restored FGF-2 mitogenic activity and internalization. Additional biochemical analyses, coimmunoprecipitation experiments, and FRET analysis showed that FGF-R1 and PDGF-Rα directly interact in vitro and in vivo and that this interaction is somehow increased in the presence of the corresponding ligands FGF-2 and PDGF-BB. These results suggest that FGF-R1/PDGF-Rα heterodimerization may represent a novel endogenous mechanism to modulate the action of these receptors and their ligands and to control endothelial cell function.

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