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Perturbation of the platelet‐derived growth factor receptor signaling by dibutyryl‐camp in human astrocytoma cells
Author(s) -
Tsai ChonHaw,
Hung LiMan,
Chen JanKan
Publication year - 1995
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041640114
Subject(s) - autophosphorylation , platelet derived growth factor receptor , receptor tyrosine kinase , tyrosine phosphorylation , tyrosine kinase , tropomyosin receptor kinase c , biology , microbiology and biotechnology , phospholipase c , ror1 , phosphorylation , signal transduction , chemistry , endocrinology , biochemistry , protein kinase a , growth factor , receptor
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_ γ1 (PLC_ γ1 ) and phosphatidylinositol 3‐kinase (PI 3‐kinase) are also suppressed in dibutyryl‐cAMP‐pretreated cells. The suppression of PLC_ γ1 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_ γ1 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. © 1995 Wiley‐Liss, Inc.