Kinetics and regulation of tyrosine phosphorylation of the platelet derived growth factor receptor.
Platelet derived growth factor (PDGF) interaction with the cells induces rapid tyrosine phosphorylation of the PDGF receptor in a dose dependent manner. At 37 degrees C phosphorylation of the receptor is followed by its dephosphorylation and internalization. It is observed that the higher the ligand concentration, the more transient is the response, and the observed kinetics are explained by a simple kinetic model. At 4 degrees C the phosphorylated form of the receptor is more stable; however, if PDGF is dissociated from the cell surface-associated ligand-receptor complexes, the receptors are rapidly dephosphorylated, indicating that phosphatases specific for phosphotyrosine groups are very active within the cells. In fact, addition of orthovanadate stabilizes the phosphorylated form of the receptor and helps in recognizing possible physiological substrates of the PDGF receptor kinase. The expression of PDGF receptors on the cell surface has been investigated under different growth conditions: a positive correlation exists between the amount of PDGF receptors and the duplication times of exponentially growing cultures. Moreover, during exponential growth the PDGF receptors are scarcely expressed, and their number increases reaching a maximal value when the population enters the stationary phase.
Alberghina
L
L
Dipartimento di Fisiologia e Biochimica Generali, Università di Milano, Italy.
Zippel
R
R
Martegani
E
E
Sturani
E
E
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D007700:Kinetics; D051379:Mice; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor; D014443:Tyrosine / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D014443:Tyrosine; D017479:Receptors, Platelet-Derived Growth Factor; D010744:Phosphoric Monoester Hydrolases