Perturbation of the platelet-derived growth factor receptor signaling by dibutyryl-cAMP in human astrocytoma cells.
It has been shown that cAMP may perturb the polypeptide growth factor-induced nuclear events. However, the possible interactions of the cAMP-protein kinase A (cAMP-PKA) and receptor tyrosine kinase pathways in the cytosol have not been fully elucidated. In this study, we use human astrocytoma cells as a model to investigate this issue. The results show that platelet-derived growth factor (PDGF)-induced receptor autophosphorylation in human astrocytoma cells is suppressed by dibutyryl-cAMP pretreatment and such suppression is not due to changes in the ligand-receptor binding properties. Further studies show that PDGF-induced tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and phosphatidylinositol 3-kinase (PI 3-kinase) are also suppressed in dibutyryl-cAMP-pretreated cells. The suppression of PLC-gamma 1 tyrosine phosphorylation was accompanied by a decreased production of water soluble inositol phosphates. In contrast, similar treatment with normal human astrocytes potentiates the tyrosine phosphorylation of PLC-gamma 1 and PI 3-kinase. The results indicate that cAMP can either negatively or positively modulate the PDGF receptor tyrosine kinase activity depending on the cell types examined.
Tsai
C H
CH
Department of Neurology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan.
Hung
L M
LM
Chen
J K
JK
D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology; D003994:Bucladesine / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases; D051966:Phospholipase C gamma; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D007527:Isoenzymes; D014443:Tyrosine; D003994:Bucladesine; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017479:Receptors, Platelet-Derived Growth Factor; D010738:Type C Phospholipases; D051966:Phospholipase C gamma