RACK1, a Protein Kinase C Anchoring Protein, Coordinates the Binding of Activated Protein Kinase C and Select Pleckstrin Homology Domains in Vitro†

Biochemistry ◽  
1999 ◽  
Vol 38 (42) ◽  
pp. 13787-13794 ◽  
Author(s):  
Manuel M. Rodriguez ◽  
Dorit Ron ◽  
Kazushige Touhara ◽  
Che-Hong Chen ◽  
Daria Mochly-Rosen
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pleckstrin Homology ◽  
Kinase C ◽  
Anchoring Protein ◽  
Homology Domains

scholarly journals Mechanism of A-kinase-anchoring protein 79 (AKAP79) and protein kinase C interaction

1999 ◽  
Vol 343 (2) ◽  
pp. 443-452 ◽  
Author(s):  
Maree C. FAUX ◽  
Emily N. ROLLINS ◽  
Amelia S. EDWARDS ◽  
Lorene K. LANGEBERG ◽  
Alexandra C. NEWTON ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Interactions ◽  
Hippocampal Neurons ◽  
Kinase Activity ◽  
Catalytic Core ◽  
Kinase C ◽  
Anchoring Protein ◽  
Arginine Residues

The A-kinase-anchoring protein AKAP79 co-ordinates the location of cAMP-dependent protein kinase, phosphatase 2B (PP2B/calcineurin) and protein kinase C (PKC) at postsynaptic sites in neurons. In this report we focus on the mechanism of interaction between AKAP79 and PKC. We show that neither lipid activators nor kinase activation are required for association with AKAP79. The anchoring protein binds and inhibits the conserved catalytic core of PKCβII. AKAP79 also associates with conventional, novel and atypical isoforms of PKC in vitro andin vivo, and immunofluorescence staining of rat hippocampal neurons demonstrates that the murine anchoring-protein homologue AKAP150 is co-distributed with PKCα/β, PKCε or PKCℓ. Binding of the AKAP79(31-52) peptide, which inhibits kinase activity, exposes the pseudosubstrate domain of PKCβII, allowing endoproteinase Arg-C proteolysis in the absence of kinase activators. Reciprocal experiments have identified two arginine residues at positions 39 and 40 that are essential for AKAP79(31-52) peptide inhibition of PKCβII. Likewise, the same mutations in the full-length anchoring protein reduced inhibition of PKCβII. Thus AKAP79 associates with multiple PKC isoforms through a mechanism involving protein-protein interactions at the catalytic core where binding of the anchoring protein inhibits kinase activity through displacement of the pseudosubstrate.

scholarly journals Interactions between Protein Kinase C and Pleckstrin Homology Domains

1997 ◽  
Vol 272 (20) ◽  
pp. 13033-13039 ◽  
Author(s):  
Libo Yao ◽  
Hidefumi Suzuki ◽  
Koichiro Ozawa ◽  
Jianbei Deng ◽  
Csaba Lehel ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pleckstrin Homology ◽  
Kinase C ◽  
Homology Domains

scholarly journals N-Acetylcysteine and α-cyano-4-hydroxycinnamic acid alter protein kinase C (PKC)-δ and PKC-ζ and diminish dysmorphogenesis in rat embryos cultured with high glucose in vitro

2007 ◽  
Vol 192 (1) ◽  
pp. 207-214 ◽  
Author(s):  
Mattias Gäreskog ◽  
Parri Wentzel
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
High Glucose ◽  
Culture Medium ◽  
Hydroxycinnamic Acid ◽  
Oxygen Species ◽  
Rat Embryos ◽  
Protein Kinase C Inhibitors ◽  
Kinase C

Malformations and growth disturbances are two- to threefold more common in infants of diabetic mothers than in offspring of non-diabetic pregnancy. Several suggestions have emerged to explain the reasons for diabetic embryopathy, including enhanced mitochondrial production of reactive oxygen species leading to altered activation of protein kinase C. This study aimed to evaluate the effect of α-cyano-4-hydroxycinnamic acid (CHC) and N-acetylcysteine (NAC) addition on morphology and activity of protein kinase C-δ and protein kinase C-ζ in rat embryos exposed to a high glucose concentration in vitro. Day 9 embryos from normal rats were cultured in 10 or 30 mM glucose concentrations with or without supplementation of CHC, NAC, or protein kinase C inhibitors specific for protein kinase C-δ and protein kinase C-ζ. Embryos were evaluated for malformations, crown rump length, and somite number. Protein kinase C-δ and protein kinase C-ζ activities were estimated by western blot by separating membranous and cytosolic fractions of the embryo. We found increased malformations and growth retardation in embryos cultured in high versus low glucose concentrations. These abnormalities were diminished when CHC and NAC or specific protein kinase C-inhibitors were added to the culture medium. The activities of embryonic protein kinase C-δ and protein kinase C-ζ were increased in the high glucose environment after 24-h culture, but were normalized by the addition of CHC and NAC as well as respective inhibitor to the culture medium. These findings suggest that mitochondrial overproduction of reactive oxygen species is involved in diabetic embryopathy. Furthermore, such overproduction may affect embryonic development, at least partly, by enhancing the activities of protein kinase C-δ and protein kinase C-ζ.

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