scholarly journals Cbl-mediated Negative Regulation of Platelet-derived Growth Factor Receptor-dependent Cell Proliferation

1999 ◽  
Vol 274 (23) ◽  
pp. 16619-16628 ◽  
Author(s):  
Sachiko Miyake ◽  
Karen P. Mullane-Robinson ◽  
Nancy L. Lill ◽  
Patrice Douillard ◽  
Hamid Band
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Negative Regulation ◽  
Platelet Derived Growth Factor ◽  
Dependent Cell

scholarly journals Evidence for glutathione involvement in platelet-derived growth-factor-mediated signal transduction

1997 ◽  
Vol 324 (3) ◽  
pp. 791-796 ◽  
Author(s):  
Stefania RIGACCI ◽  
Teresa IANTOMASI ◽  
Patrizia MARRACCINI ◽  
Andrea BERTI ◽  
Maria Teresa VINCENZINI ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Platelet Derived Growth Factor ◽  
Glutathione Depletion ◽  
Physiological Processes ◽  
Buthionine Sulphoximine ◽  
Precise Relationship

Recent studies show that glutathione, while being involved in the well-known physiological processes of amino acid transport and detoxification, can also play a part in cell proliferation events. Cell treatment with l-buthionine sulphoximine, which causes glutathione depletion, is accompanied by a decrease in cell proliferation. At present no precise relationship between this thiol and any critical intermediate of the mitogenic cascade has been proved. In this study, conducted on NIH/3T3 murine fibroblasts, we demonstrate a strict correlation between glutathione levels and platelet-derived growth-factor-receptor activation in response to stimulation and cell proliferation. The receptor autophosphorylation is severely impaired at low glutathione cellular levels. The interaction of glutathione with this growth-factor receptor in vivo, while being rather specific, is complex and may involve both cytosolic and extracellular receptor domains.

scholarly journals Activation of Src Family Members Is Not Required for the Platelet-Derived Growth Factor β Receptor To Initiate Mitogenesis

1998 ◽  
Vol 18 (4) ◽  
pp. 2014-2022 ◽  
Author(s):  
Kris A. DeMali ◽  
Andrius Kazlauskas
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Platelet Derived Growth Factor ◽  
Maximal Activation ◽  
Associated Proteins ◽  
Dependent Cell ◽  
Β Receptor ◽  
Stimulation Of

ABSTRACT The basal activity of Src family kinases is readily detectable throughout the cell cycle and increases by two- to fivefold upon acute stimulation of cells with growth factors such as platelet-derived growth factor. Previous reports have demonstrated a requirement for Src activity for the G1/S and G2/M transitions. With a chimeric α-β PDGF receptor (PDGFR) expressed in fibroblasts, we have investigated the importance of the PDGF-mediated increase in Src activity at the G0/G1 transition for subsequent cell cycle events. A mutant PDGFR chimera that was not able to detectably associate with or activate Src was compromised in its ability to mediate tyrosine phosphorylation of receptor-associated signaling molecules and initiated a submaximal activation of Erk. In contrast to these early cell cycle events, later responses such as entry of cells into S phase and cell proliferation proceeded normally when Src activity did not increase following acute stimulation with PDGF. We conclude that the initial burst of Src activity is required for efficient tyrosine phosphorylation of receptor-associated proteins such as PLCγ, RasGAP, Shc, and SHP-2 and for maximal activation of Erk. Surprisingly, these events are not required for PDGF-dependent cell proliferation. Finally, later cell cycle events do not require that Src be activated at the G0/G1 transition and leave open the possibility that events such as the G1/S transition require the basal Src activity and/or activation of Src at later times in G1.

scholarly journals NHERF Links the N-Cadherin/Catenin Complex to the Platelet-derived Growth Factor Receptor to Modulate the Actin Cytoskeleton and Regulate Cell Motility

2007 ◽  
Vol 18 (4) ◽  
pp. 1220-1232 ◽  
Author(s):  
Christopher S. Theisen ◽  
James K. Wahl ◽  
Keith R. Johnson ◽  
Margaret J. Wheelock
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Kinase Inhibitor ◽  
Pdz Domain ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Platelet Derived Growth Factor ◽  
Binding Motif ◽  
Pdz Domains ◽  
Dependent Cell

Using phage display, we identified Na+/H+ exchanger regulatory factor (NHERF)-2 as a novel binding partner for the cadherin-associated protein, β-catenin. We showed that the second of two PSD-95/Dlg/ZO-1 (PDZ) domains of NHERF interacts with a PDZ-binding motif at the very carboxy terminus of β-catenin. N-cadherin expression has been shown to induce motility in a number of cell types. The first PDZ domain of NHERF is known to bind platelet-derived growth factor-receptor β (PDGF-Rβ), and the interaction of PDGF-Rβ with NHERF leads to enhanced cell spreading and motility. Here we show that β-catenin and N-cadherin are in a complex with NHERF and PDGF-Rβ at membrane ruffles in the highly invasive fibrosarcoma cell line HT1080. Using a stable short hairpin RNA system, we showed that HT1080 cells knocked down for either N-cadherin or NHERF had impaired ability to migrate into the wounded area in a scratch assay, similar to cells treated with a PDGF-R kinase inhibitor. Cells expressing a mutant NHERF that is unable to associate with β-catenin had increased stress fibers, reduced lamellipodia, and impaired cell migration. Using HeLa cells, which express little to no PDGF-R, we introduced PDGF-Rβ and showed that it coimmunoprecipitates with N-cadherin and that PDGF-dependent cell migration was reduced in these cells when we knocked-down expression of N-cadherin or NHERF. These studies implicate N-cadherin and β-catenin in cell migration via PDGF-R–mediated signaling through the scaffolding molecule NHERF.

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