Compendium of the most significant studies with reference to properties, intake, effects.

Barrasa MI, Harel NY, Alwine JC. The phosphorylation status of the serine-rich region of the human cytomegalovirus 86-kilodalton major immediate-early protein IE2/IEP86 affects temporal viral gene expression. J Virol. 2005 Feb;79(3):1428-37. doi: 10.1128/JVI.79.3.1428-1437.2005. 

Abstract. The 86-kDa major immediate-early protein (IE2/IEP86) of human cytomegalovirus (HCMV) contains a serine-rich region (amino acids 258 to 275) with several consensus casein kinase II (CKII) sites. We performed extensive mutational analysis of this region, changing serines to alternating alanines and glycines. Mutation of the serines between amino acids 266 and 275 eliminated in vitro phosphorylation by CKII. In vitro CKII phosphorylation of the serines between amino acids 266 and 269 or between amino acids 271 and 275 inhibited the ability of IE2/IEP86 to bind to TATA-binding protein.

Menou A, Duitman J, Flajolet P, Sallenave JM, Mailleux AA, Crestani B. Human airway trypsin-like protease, a serine protease involved in respiratory diseases. Am J Physiol Lung Cell Mol Physiol. 2017 May 1;312(5):L657-L668. doi: 10.1152/ajplung.00509.2016.

Abstract. More than 2% of all human genes are coding for a complex system of more than 700 proteases and protease inhibitors. Among them, serine proteases play extraordinary, diverse functions in different physiological and pathological processes. 

Pariser H, Herradon G, Ezquerra L, Perez-Pinera P, Deuel TF. Pleiotrophin regulates serine phosphorylation and the cellular distribution of beta-adducin through activation of protein kinase C. Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12407-12. doi: 10.1073/pnas.0505901102. 

Abstract. Pleiotrophin (PTN) was found to regulate tyrosine phosphorylation of beta-adducin through the PTN/receptor protein tyrosine phosphatase (RPTP)beta/zeta signaling pathway. We now demonstrate that PTN stimulates the phosphorylation of serines 713 and 726 in the myristoylated alanine-rich protein kinase (PK) C substrate domain of beta-adducin through activation of either PKC alpha or beta. We also demonstrate that PTN stimulates translocation of phosphoserine 713 and 726 beta-adducin either to nuclei, where it associates with nuclear chromatin and with centrioles of dividing cells, or to a membrane-associated site, depending on the phase of cell growth. 

Le Douce J, Maugard M, Veran J, Matos M, Jégo P, Vigneron PA, Faivre E, Toussay X, Vandenberghe M, Balbastre Y, Piquet J, Guiot E, Tran NT, Taverna M, Marinesco S, Koyanagi A, Furuya S, Gaudin-Guérif M, Goutal S, Ghettas A, Pruvost A, Bemelmans AP, Gaillard MC, Cambon K, Stimmer L, Sazdovitch V, Duyckaerts C, Knott G, Hérard AS, Delzescaux T, Hantraye P, Brouillet E, Cauli B, Oliet SHR, Panatier A, Bonvento G. Impairment of Glycolysis-Derived l-Serine Production in Astrocytes Contributes to Cognitive Deficits in Alzheimer's Disease. Cell Metab. 2020 Mar 3;31(3):503-517.e8. doi: 10.1016/j.cmet.2020.02.004.

Abstract. Here, we show that the astrocytic l-serine biosynthesis pathway, which branches from glycolysis, is impaired in young  Alzheimer's disease (AD) mice and in AD patients. l-serine is the precursor of d-serine, a co-agonist of synaptic NMDA receptors (NMDARs) required for synaptic plasticity.

Baumgart F, Rodríguez-Crespo I. D-amino acids in the brain: the biochemistry of brain serine racemase. FEBS J. 2008 Jul;275(14):3538-45. doi: 10.1111/j.1742-4658.2008.06517.x. 

Abstract. It has been recently established that in various brain regions D-serine, the product of serine racemase, occupies the so-called 'glycine site' within N-methyl D-aspartate receptors. Mammalian brain serine racemase is a pyridoxal-5' phosphate-containing enzyme that catalyzes the racemization of L-serine to D-serine. It has also been shown to catalyze the alpha,beta-elimination of water from L-serine or D-serine to form pyruvate and ammonia. 

Yang JH, Wada A, Yoshida K, Miyoshi Y, Sayano T, Esaki K, Kinoshita MO, Tomonaga S, Azuma N, Watanabe M, Hamase K, Zaitsu K, Machida T, Messing A, Itohara S, Hirabayashi Y, Furuya S. Brain-specific Phgdh deletion reveals a pivotal role for L-serine biosynthesis in controlling the level of D-serine, an N-methyl-D-aspartate receptor co-agonist, in adult brain. J Biol Chem. 2010 Dec 31;285(53):41380-90. doi: 10.1074/jbc.M110.187443.

Abstract. The present study provides definitive proof that L-serine-synthesized endogenously via the phosphorylated pathway is a key rate-limiting factor for maintaining steady-state levels of D-serine in adult brain. Furthermore, NMDA-evoked transcription of Arc, an immediate early gene, was diminished in the hippocampus of conditional knock-out mice. Thus, this study demonstrates that in mature neuronal circuits L-serine availability determines the rate of D-serine synthesis in the forebrain and controls NMDA receptor function at least in the hippocampus.

Ai X, Yan J, Pogwizd SM. Serine-threonine protein phosphatase regulation of Cx43 dephosphorylation in arrhythmogenic disorders. Cell Signal. 2021 Oct;86:110070. doi: 10.1016/j.cellsig.2021.110070.

Abstract.  The focus of this review is to introduce serine-threonine protein phosphatase regulation of Cx43 phosphorylation state and cell-to-cell communication, and its impact on arrhythmogenesis in the setting of chronic heart failure and myocardial ischemia, as well as on atrial fibrillation. We also discuss the therapeutic potential of modulating protein phosphatases to treat arrhythmias in these clinical settings.

Morioka M, Kawano T, Yano S, Kai Y, Tsuiki H, Yoshinaga Y, Matsumoto J, Maeda T, Hamada J, Yamamoto H, Fukunaga K, Kuratsu J. Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia. Biochem Biophys Res Commun. 2006 Aug 18;347(1):273-8. doi: 10.1016/j.bbrc.2006.06.096.

Abstract. We examined the phosphorylation state of tau factor in hippocampal delayed neuronal death (DND) after transient forebrain ischemia. A transient phosphorylation increase at serine 199/202 but not serine 396 of tau factor after transient ischemia was clearly observed. Intraventricular injections of olomoucine and U-0126 (CDK5 and MAP kinase inhibitors, respectively) inhibited hyperphosphorylation.