Activation of phospholipase D induced by platelet-derived growth factor is dependent upon the level of phospholipase C-gamma 1
| Autor: | Hee Sook Kim, Pann-Ghill Suh, Sung Ho Ryu, Young Han Lee, Jin-Keon Pai |
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| Rok vydání: | 1994 |
| Předmět: |
Platelet-derived growth factor
Phospholipase D Tyrosine phosphorylation Cell Biology Phospholipase C gamma Biology Biochemistry Molecular biology 3T3 cells Cell biology enzymes and coenzymes (carbohydrates) chemistry.chemical_compound medicine.anatomical_structure chemistry biology.protein medicine lipids (amino acids peptides and proteins) Molecular Biology Tyrosine kinase Protein kinase C Platelet-derived growth factor receptor |
| Zdroj: | Journal of Biological Chemistry. 269:26842-26847 |
| ISSN: | 0021-9258 |
| Popis: | The mechanism of phospholipase D (PLD) activation by platelet-derived growth factor (PDGF) was examined using a NIH 3T3 fibroblast cell line (3T3-gamma 1) that stably overexpresses PLC-gamma 1 isozyme. Immunoblot analysis revealed that 3T3-gamma 1 cells contained about 10-fold more PLC-gamma 1 than a control cell line (3T3-C) transfected with expression vector lacking PLC-gamma 1 cDNA. PDGF-stimulated PLD activation was 10-fold greater in 3T3-gamma 1 cells than in 3T3-C cells, indicating that PLD activation is dependent upon the level of PLC-gamma 1. Phorbol 12-myristate 13-acetate (PMA) treatment increased PLD activity to a similar extent in both 3T3-gamma 1 cells and control cells. Pretreatment with tyrosine kinase inhibitors including staurosporine and genistein decreased PLD activity by 82.6% and 87.2%, respectively, and completely blocked tyrosine phosphorylation of PDGF receptor and PLC-gamma 1 in 3T3-gamma 1 cells stimulated with PDGF. Moreover, down-regulation of protein kinase C by pretreatment of PMA caused complete inhibition of PDGF- and PMA-stimulated PLD activation. Therefore, these results suggest that PDGF-induced PLD activation may be a consequence of primary stimulation of PLC-gamma 1 and that PLD may play a role downstream from PLC-gamma 1 in PDGF-triggered mitogenesis. |
| Databáze: | OpenAIRE |
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