Kinases and Phosphatases

14 pages, 8785 KiB

Open AccessReview

Overview of Capillary Electrophoresis Analysis of Alkaline Phosphatase (ALP) with Emphasis on Post-Translational Modifications (PTMs)

by Thanih Balbaied and Eric Moore

Kinases Phosphatases 2023, 1(3), 206-219; https://doi.org/10.3390/kinasesphosphatases1030013 - 15 Sep 2023

Viewed by 1941

Abstract

Alkaline phosphatase is a vital enzyme used in separation studies and as a biomarker for liver, bone, and certain cancer conditions. Its stability and specific properties enable insights into enzyme behavior, aiding in the development of detection methods with broader applications in various scientific fields. Alkaline phosphatase has four main isoenzymes: GCAP, IAP, PLAP, and TNAP, each with distinct roles. TNAP is found in the liver, kidney, and bones, playing a role in bone mineralization. The functions of the other isoenzymes are not fully known. Separation techniques like electrophoresis and chromatography are valuable for studying enzymes and proteins, revealing insights into their structure and function in pharmaceutical research and PTM studies. The main goal of this review paper is to thoroughly evaluate how capillary electrophoresis is applied to analyze alkaline phosphatase. It seeks to investigate the latest advancements in capillary electrophoresis and how they can improve the sensitivity, selectivity, and efficiency of alkaline phosphatase analysis. Full article

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25 pages, 1583 KiB

Open AccessReview

From Kinases to Diseases: Investigating the Role of AMPK in Human Pathologies

by Verónica Rey and Isaac Tamargo-Gómez

Kinases Phosphatases 2023, 1(3), 181-205; https://doi.org/10.3390/kinasesphosphatases1030012 - 01 Aug 2023

Cited by 3 | Viewed by 2480

Abstract

Adenosine Monophosphate-Activated Protein Kinase (AMPK) is the major conserved regulator of cellular metabolism in eukaryotic cells, from yeast to mammals. Given its pivotal role, it is not surprising that alterations in its function may contribute to the pathogenesis of numerous human diseases. Indeed, AMPK has become a promising therapeutic target for several pathologies. In this context, significant efforts have been dedicated to discovering new pharmacological agents capable of activating AMPK based on next-generation sequencing (NGS) technology and personalized medicine. Thanks to computational methodologies and high-throughput screening, the identification of small molecules and compounds with the potential to directly activate AMPK or modulate its intricate signaling network has become viable. However, the most widely used drug to activate AMPK in human patients is still metformin, which has shown promising results in the treatment of various diseases, such as type II diabetes, atherosclerosis, Alzheimer’s disease, Huntington’s disease, and several types of cancer. In this review, we present a comprehensive analysis of the involvement of AMPK in human pathology, emphasizing its significant potential as a therapeutic target. Full article

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14 pages, 2239 KiB

Open AccessArticle

Phosphorylation of Ack1 by the Receptor Tyrosine Kinase Mer

by Samantha Y. Hayashi, Barbara P. Craddock and W. Todd Miller

Kinases Phosphatases 2023, 1(3), 167-180; https://doi.org/10.3390/kinasesphosphatases1030011 - 10 Jul 2023

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Abstract

Ack1 is a nonreceptor tyrosine kinase that is associated with cellular proliferation and survival. The receptor tyrosine kinase Mer, a member of the TAM family of receptors, has previously been reported to be an upstream activator of Ack1 kinase. The mechanism linking the two kinases, however, has not been investigated. We confirmed that Ack1 and Mer interact by co-immunoprecipitation experiments and found that Mer expression led to increased Ack1 activity. The effect on Ack1 was dependent on the kinase activity of Mer, whereas mutation of the Mer C-terminal tyrosines Y867 and Y924 did not significantly decrease the ability of Mer to activate Ack1. Ack1 possesses a Mig6 Homology Region (MHR) that contains adjacent regulatory tyrosines (Y859 and Y860). Using synthetic peptides, we showed that Mer preferentially binds and phosphorylates the MHR sequence containing phosphorylated pY860, as compared to the pY859 sequence. This suggested the possibility of sequential phosphorylation within the MHR of Ack1, as has been observed previously for other kinases. In cells co-expressing Mer and Ack1 MHR mutants, the Y859F mutant had higher activity than the Y860F mutant, consistent with this model. The interaction between Mer and Ack1 could play a role in immune cell signaling in normal physiology and could also contribute to the hyperactivation of Ack1 in prostate cancer and other tumors. Full article

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16 pages, 3244 KiB

Open AccessReview

Phosphorylation of Metabolites Involved in Salvage Pathways for Isoprenoid Biosynthesis in Plants

by Andréa Hemmerlin

Kinases Phosphatases 2023, 1(3), 151-166; https://doi.org/10.3390/kinasesphosphatases1030010 - 03 Jul 2023

Cited by 1 | Viewed by 1985

Abstract

The recycling of metabolic products is a major way to reduce the energy cost of de novo biosynthesis. The salvage pathways involved not only regain a metabolic product but also generate additional molecules that might serve specific physiological, developmental and/or defensive functions. The isoprenoid pathway is a perfect example of a fine-regulated biosynthetic pathway, by virtue of the large number of molecules with different functions that must be synthesized simultaneously. Additionally, isoprenoid salvage pathways have been characterized. Thus, to produce isoprenoid precursors such as farnesyl diphosphate or phytyl diphosphate, short-chain isoprenols recovered from end-chain metabolites are phosphorylated. In the first instance, the so-called FPP-salvage machinery recycles farnesyl diphosphate from proteolyzed farnesylated proteins. In a second example, phytyl diphosphate is recycled from degraded chlorophyll, to be used for the biosynthesis of vitamin E. Both compounds are recovered as alcohols and require two phosphorylation events to be reactivated and reintegrated into the isoprenoid biosynthetic pathway. This review covers current knowledge of isoprenol biosynthesis, metabolism and function, as well as potential benefits of recycling pathways for plants, with a particular focus on stress responses. Full article

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Kinases Phosphatases, Volume 1, Issue 3 (September 2023) – 4 articles

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