PDE4-regulated cAMP degradation controls the assembly of integrin-dependent actin adhesion structures and REF52 cell migration.

Plating of REF52 cells onto extracellular matrix components leads to the formation of integrin-dependent actin adhesion microspikes. We show that the formation of these structures is sensitive to chemical agents that regulate cAMP levels, such as forskolin and IBMX. In particular, by using the specific inhibitor rolipram, we identify the PDE4 family of cAMP-specific phosphodiesterases as critical regulators of this process.

Mitogen-activated protein kinase kinase 7 is activated during low potassium-induced apoptosis in rat cerebellar granule neurons.

A stress-activated protein kinase pathway comprising mitogen-activated protein kinase kinases (MKKs), c-Jun N-terminal kinase (JNK) and the transcription factor c-Jun is implicated in neuronal apoptosis. Using an immune-complex kinase assay, we measured the activation of MKK4 and MKK7 in low potassium (LK)-induced apoptosis of rat cerebellar granule neurons (CGN). MKK7, but not MKK4, was activated within the first 4-6 h in four independent sets of 14-h CGN apoptosis time-courses.