Protein kinase A activity is required for depolarization-induced proline-rich tyrosine kinase 2 and mitogen-activated protein kinase activation in PC12 cells.
Protein kinase A (PKA) plays an essential role in the depolarization-induced c-fos expression in PC12 cells although the exact mechanism is unknown. Here we demonstrate that PKA is required for depolarization-induced activation of both extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase in PC12 cells. In addition, we have found that the depolarization-induced tyrosine phosphorylation of proline-rich tyrosine kinase (PYK) 2, a key calcium-sensitive upstream mediator of MAP kinase activation, is profoundly blocked by PKA inhibition. In contrast to the depolarization-induced signaling, the ERK and PYK2 activation by bradykinin (1 microM), a G-protein coupled receptor agonist, was not blocked by PKA inhibition. These findings suggest that PKA inhibition prevents depolarization-induced PYK2/MAP kinase pathway activation, thereby inhibiting the early gene expression.
Department of Anatomy, College of Medicine, Inje University, 633-165, Gaegum-dong, Pusanjin-Gu, 614-735, Pusan, South Korea.
J H
JH
Park
J K
JK
Park
K W
KW
Bae
H T
HT
Park
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D004790:Enzyme Induction; D051418:Focal Adhesion Kinase 2; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000378:metabolism; D016716:PC12 Cells / Q000201:enzymology* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats
D016760:Proto-Oncogene Proteins c-fos; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; C496054:Ptk2b protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium