Home
Resources
Publications
Protein Kinase G type-Ialpha Phosphorylates the Apoptosis-Regulating Protein Bad at Serine 155 and Protects Against Apoptosis in N1E-115 Cells

Protein Kinase G type-Ialpha Phosphorylates the Apoptosis-Regulating Protein Bad at Serine 155 and Protects Against Apoptosis in N1E-115 Cells

Mary G Johlfs, Ronald R Fiscus

Neurochem Int. 2010 Mar;56(4):546-53.

PMID: 20043968

Abstract:

Previous studies from our laboratory have shown that the cGMP/protein kinase G (PKG) signaling pathway plays an essential role in preventing spontaneous apoptosis in neural cells; however, the mechanism is not understood. A potential downstream target of PKG is the apoptosis-regulating protein Bad, which contains a sequence around its serine 155 (ser155 in mouse Bad, equivalent to ser118 in human Bad) predicted to be a consensus motif for PKG-catalyzed phosphorylation. Using both in vitro and cell-based experiments, we determined if PKG phosphorylates Bad at ser155 and if blocking/stimulating PKG-catalyzed Bad phosphorylation causes pro-apoptotic/anti-apoptotic responses. Recombinant PKG type-Ialpha (PKG-Ialpha) was found to directly phosphorylate recombinant Bad at ser155 in vitro. In N1E-115 mouse neural cells, which naturally express PKG-Ialpha as the predominant PKG isoform, addition of 8-Br-cGMP (0.1-1.0 mM), a cell-permeable direct PKG-Ialpha activator, increased ser155 phosphorylation of Bad. ODQ (50 microM), a soluble guanylyl cyclase inhibitor that lowers cGMP/PKG activity, decreased serum-induced ser155 phosphorylation of Bad and induced apoptosis in N1E-115 cells. Treatment with DT-2 and DT-3, selective PKG-Ialpha inhibitors, both decreased Bad ser155 phosphorylation and induced apoptosis. The data indicate that PKG-Ialpha directly phosphorylates Bad at ser155, which may participate in cGMP/PKG-induced anti-apoptotic/cytoprotective effects in neural cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415610	PKG Iα Inhibitor, Cell-Permeable			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: