Intracellular Peptide Turnover: Properties and Physiological Significance of the Major Peptide Hydrolases of Brain Cytosol
Gerard O’Cuinn in Metabolism of Brain Peptides, 2020
Hui et al. provided evidence for two isozymes of c-AAP in chicken brain132. Two forms of the soluble enzyme designated SI and SII were separated by Bio Gel HTP® chromatography. SI is a monomer of 105,000 whereas SII is composed of two polypeptides of 100,000 and 25,000. The catalytic properties of both forms are similar, however tryptic peptide maps differ. Amino acid sequence of fragments was reported as not identical but homologous. Interestingly, sequence homology to a brain specific 14-3-3 protein was found. This protein is a protein kinase activator of tyrosine and tryptophan hydroxylases. The possible regulation of c-AAP has not been extensively explored. The purified monkey brain enzyme was stimulated four-fold by 1mM ATP + 4 mM Mg++133. This effect was due to a change in the Vmax of the enzyme. However phosphorylation was not the underlying mechanism since these investigators found a similar effect with non-hydrolyzable analogs of ATP and could find no evidence for phosphorylation. It was proposed that ATP activates by reversibly binding to a site on the enzyme. The enzyme can also be phosphorylated by the catalytic subunit of cAMP-dependent protein kinase. In this case, phosphorylation leads to a decrease in enzymatic activity. It is not known how these changes relate to the regulation of c-AAP in vivo.
Homeostasis of Dopamine
Nira Ben-Jonathan in Dopamine, 2020
The processes of DA synthesis by TH and DDC and its transport into storage vesicles by VMATs have long been viewed as two separate and independent events. However, several lines of evidence, employing co-immunoprecipitation, overexpression, mutagenesis, and in vitro binding assays, revealed that VMAT2 and the DA biosynthetic enzymes are physically and functionally coupled at the synaptic vesicle membrane [69]. The coupling complex also includes scaffolding proteins such as 14-3-3 protein and synuclein. Although TH is commonly considered a cytosolic enzyme, it exists in both cytosolic and membrane-bound forms. Cytosolic TH is enriched in neuronal somato–dendritic compartments of the substantia nigra and ventral tegmental area, whereas membrane-bound TH is more common in brain areas enriched in axon terminals (e.g., striatum and nucleus accumbens).
Neuroprotection
Glenn J. Jaffe, Paul Ashton, P. Andrew Pearson in Intraocular Drug Delivery, 2006
Several lines of evidence suggest that an additional, finer level of control over Bcl-2–Bax interaction may be achieved by the participation of related family members such as Bad. In the retina, Bad is expressed predominantly by ganglion cells (42). Normally, Bad is sequestered in the cytoplasm by the 14-3-3 class of proteins. Extracellular growth or survival factors appear to affect survival, in part, through activation of a pathway involving phosphoinositide 3 kinase (PI3-K) (43,44). PI3-K, in turn, activates a serine–threonine protein kinase, Akt, that phosphorylates Bad (45–47) and promotes its association with the 14-3-3 protein family (29). Thus sequestered, Bad is unable to prevent the heterodimerization of Bcl-XL with Bax, favoring cell survival.
Quercetin protects cardiomyocytes against doxorubicin-induced toxicity by suppressing oxidative stress and improving mitochondrial function via 14-3-3γ
Published in Toxicology Mechanisms and Methods, 2019
Xuanying Chen, Xiaoping Peng, Yong Luo, Jiegen You, Dong Yin, Qiang Xu, Huan He, Ming He
14-3-3γ is one of the 14-3-3 protein family members, which belong to a group of highly conserved 30 kDa acidic proteins that are expressed in a wide variety of organisms and tissues (Aitken 2006). 14-3-3 s participate in the regulation of diverse biological processes such as cell division, signal transduction, and apoptosis by interacting with their effector proteins (Fu et al. 2000; van Hemert et al. 2001). 14-3-3 s also play an important role in cardiac protection (Allouis et al. 2006; Lynn et al. 2008). Our previous studies confirmed that two members of the 14-3-3 protein family members, 14-3-3η and 14-3-3γ, are involved in myocardial injury and protection; 14-3-3η is involved in ischemia/hypoxia injury, whereas 14-3-3γ is involved in infection-related injury (He et al. 2006; Chen et al. 2007; Liu et al. 2014; He et al. 2018; Huang et al. 2018). In preliminary experiments, Que increased the expression of 14-3-3γ.
14-3-3 proteins at the crossroads of neurodevelopment and schizophrenia
Published in The World Journal of Biological Psychiatry, 2022
André S. L. M. Antunes, Verônica M. Saia-Cereda, Fernanda Crunfli, Daniel Martins-de-Souza
The 14-3-3 protein family is ubiquitously expressed in all eukaryotic organisms, making up to 1% of the total protein content in the mammalian brain. In mammals, the family consists of seven homologous, small (∼30 kDa) and acidic proteins encoded by separate genes (reviewed in Fu et al. 2000). They have an extremely rigid structure and form a highly helical, cup-shaped dimer with the exception of their flexible carboxyl-terminal region, which changes its structure upon phosphorylation (Bridges and Moorhead 2005). 14-3-3 proteins function as homo- and heterodimers dimers with each monomer possessing phosphoserine or phosphothreonine binding motifs that are able to associate with several protein targets, such as phosphatases, transcription factors, transmembrane receptors and kinases (Pozuelo Rubio et al. 2004; Fan et al. 2019).
Serum 14-3-3η is a Marker that Complements Current Biomarkers for the Diagnosis of RA: Evidence from a Meta-analysis
Published in Immunological Investigations, 2022
Yue Wu, Ziwei Dai, Haili Wang, Hong Wang, Lingling Wu, Huayun Ling, Ying Zhu, Dongqing Ye, Bin Wang
The 14-3-3 protein was discovered in the neuronal proteins extracted from cattle brain tissues in 1976, there are 7 isoforms (α/β, ε, γ, η, τ, ζ, σ)(Maksymowych et al. 2014b). These proteins have a cup-shaped “amphipathic groove” that can interact with more than 200 proteins and participate in the regulation of a variety of important cell activities, including protein trafficking, cell cycle regulation, signal transduction, tumorigenesis, etc. (Maksymowych et al. 2014b; Zeng and Tan. 2018). Kilani et al. found that 14-3-3 protein subtypes were correlated with MMP-1 and MMP-3 (The members of matrix metalloproteinases (MMPs) which play an important role in degrading cartilage matrix), and their experimental results showed that the levels of 14-3-3η and 14-3-3-3γ were very high in the serum and synovial fluid (SF) of RA patients, especially in SF (Kilani et al. 2007). Another study showed that 14-3-3η levels in serum and SF of RA patients were related to radiological damage (Hammam et al. 2020). In addition, 14-3-3η levels were also related to disease activity in RA patients (Hirata et al. 2015).
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