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 mu M), 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. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.