scholarly journals Enhancement of Glomerular Platelet-Derived Growth Factor β-Receptor Tyrosine Phosphorylation in Hypertensive Rats and Its Inhibition by Calcium Channel Blocker

2002 ◽  
Vol 25 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Yumei ZHAN ◽  
Shokei KIM ◽  
Hitomi KAWANO ◽  
Hiroshi IWAO
Keyword(s):  
Growth Factor ◽  
Calcium Channel ◽  
Tyrosine Phosphorylation ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Platelet Derived Growth Factor ◽  
Hypertensive Rats ◽  
Β Receptor

scholarly journals Site-Selective Regulation of Platelet-Derived Growth Factor β Receptor Tyrosine Phosphorylation by T-Cell Protein Tyrosine Phosphatase

2004 ◽  
Vol 24 (5) ◽  
pp. 2190-2201 ◽  
Author(s):  
Camilla Persson ◽  
Catrine Sävenhed ◽  
Annie Bourdeau ◽  
Michel L. Tremblay ◽  
Boyka Markova ◽  
...  
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Platelet Derived Growth Factor ◽  
Tyrosine Kinase Receptors ◽  
Protein Tyrosine ◽  
Phospholipase Cγ1 ◽  
Β Receptor ◽  
Ptp 1B

ABSTRACT The platelet-derived growth factor (PDGF) β receptor mediates mitogenic and chemotactic signals. Like other tyrosine kinase receptors, the PDGF β receptor is negatively regulated by protein tyrosine phosphatases (PTPs). To explore whether T-cell PTP (TC-PTP) negatively regulates the PDGF β receptor, we compared PDGF β receptor tyrosine phosphorylation in wild-type and TC-PTP knockout (ko) mouse embryos. PDGF β receptors were hyperphosphorylated in TC-PTP ko embryos. Fivefold-higher ligand-induced receptor phosphorylation was observed in TC-PTP ko mouse embryo fibroblasts (MEFs) as well. Reexpression of TC-PTP partly abolished this difference. As determined with site-specific phosphotyrosine antibodies, the extent of hyperphosphorylation varied among different autophosphorylation sites. The phospholipase Cγ1 binding site Y1021, previously implicated in chemotaxis, displayed the largest increase in phosphorylation. The increase in Y1021 phosphorylation was accompanied by increased phospholipase Cγ1 activity and migratory hyperresponsiveness to PDGF. PDGF β receptor tyrosine phosphorylation in PTP-1B ko MEFs but not in PTPε ko MEFs was also higher than that in control cells. This increase occurred with a site distribution different from that seen after TC-PTP depletion. PDGF-induced migration was not increased in PTP-1B ko cells. In summary, our findings identify TC-PTP as a previously unrecognized negative regulator of PDGF β receptor signaling and support the general notion that PTPs display site selectivity in their action on tyrosine kinase receptors.

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.

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