Control of Protein Kinase C Activity, Phorbol Ester-induced Cytoskeletal Remodeling, and Cell Survival Signals by the Scaffolding Protein SSeCKS/GRAVIN/AKAP12

Abstract

Background: SSeCKS/GRAVIN/AKAP12 is a major protein kinase C substrate and binding protein.Results: SSeCKS binding of PKC via two homologous domains is required for attenuation of PKC activity and transduction of phorbol ester-induced cytoskeletal remodeling and survival signals. Conclusion: SSeCKS controls PKC signaling via direct scaffolding interactions. Significance: PKC signaling is regulated by the spatiotemporal scaffolding activity of SSeCKS.

AKAP signaling complexes: pointing towards the next generation of therapeutic targets?

“…Gravin association with PKC occurs through direct binding of two homologous motifs resulting in kinase inhibition [40, 41]. Cellular confluence increases Gravin-PKC association, while simultaneously decreasing PKC activity.…”

Crude extract of Euphorbia formosana inhibits the migration and invasion of DU145 human prostate cancer cells: The role of matrix metalloproteinase-2/9 inhibition via the MAPK signaling pathway

“…Mitogen-activated protein kinase (MAPK) signaling contributes to human cancer cell migration, invasion and metastasis (16)(17)(18). The molecular mechanics of cancer cell migration Crude extract of Euphorbia formosana inhibits the migration and invasion of DU145 human prostate cancer cells: The role of matrix metalloproteinase-2/9 inhibition via the MAPK signaling pathway has been reported to involve cell cytoskeletal remodeling and focal adhesion dynamics (19,20). Matrix metalloproteinases (MMPs) are important in cell growth, angiogenesis, invasion and metastasis of cancer cells (16,(21)(22)(23).…”

New Insights into Phospholipase D and Sphingosine Kinase Activation in Arabidopsis

“…This is supported by the observation that diacylglycerol, which is structurally similar to PA but lacking the phosphate group did not activate SPHKs (Olivera et al, 1996). The situation appears to differ in the case of A. thaliana SPHK1 and SPHK2 as these enzymes do not appear to interact with other phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, lysophosphatidylcholine, and lysophosphatidylethanolamine (Guo et al, 2011). In contrast to mammalian SPHK1 and SPHK2 that are localized mainly in the cytosol and the nucleus, respectively, A. thaliana SPHK1 and SPHK2 are primarily associated with the tonoplast (Marion et al, 2008; Guo et al, 2011), and thus it remains to be determined if their activation by PA only may be due to their tonoplastic localization.…”

“…The situation appears to differ in the case of A. thaliana SPHK1 and SPHK2 as these enzymes do not appear to interact with other phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, lysophosphatidylcholine, and lysophosphatidylethanolamine (Guo et al, 2011). In contrast to mammalian SPHK1 and SPHK2 that are localized mainly in the cytosol and the nucleus, respectively, A. thaliana SPHK1 and SPHK2 are primarily associated with the tonoplast (Marion et al, 2008; Guo et al, 2011), and thus it remains to be determined if their activation by PA only may be due to their tonoplastic localization. Given the diversity in phospholipid classes and species in eukaryotic cells, it will be interesting, while at the same time challenging, to determine the effects of particular phospholipids on plant SPHK activities, and Wang and co-workers have initiated work in this regard with respect to different PA species (Guo et al, 2011).…”

“…In contrast to mammalian SPHK1 and SPHK2 that are localized mainly in the cytosol and the nucleus, respectively, A. thaliana SPHK1 and SPHK2 are primarily associated with the tonoplast (Marion et al, 2008; Guo et al, 2011), and thus it remains to be determined if their activation by PA only may be due to their tonoplastic localization. Given the diversity in phospholipid classes and species in eukaryotic cells, it will be interesting, while at the same time challenging, to determine the effects of particular phospholipids on plant SPHK activities, and Wang and co-workers have initiated work in this regard with respect to different PA species (Guo et al, 2011). Additionally, it can be speculated that PA targets (see this review by Guo and Wang) can phosphorylate SPHKs, leading to their activation as previously shown in mammals (Pitson, 2010).…”