Molecular basis for the integration of inositol phosphate signaling pathways via human ITPK1

Shears, Stephen B.

doi:10.1016/j.advenzreg.2008.12.008

Cited by 21 publications

(19 citation statements)

References 80 publications

(133 reference statements)

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“…If Ins(1,4,5)P 3 is the substrate, Ins(1,4,)P 2 is produced, which is dephosphorylated further and ultimately re-incorporated into new inositol lipids [17]. If Ins(1,3,4,5)P 4 is the substrate, Ins(1,3,4)P 3 is produced; the fate of Ins(1,3,4)P 3 varies among cells, and involves both kinase and phosphatase pathways [211] third messenger by binding to protein targets in cells, and the identification of physiological targets for Ins(1,3,4,5)P 4 is an active area of current research [10][11][12].…”

Section: Metabolism Of Inositol Trisphosphatementioning

confidence: 99%

Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling

Schell

2010

Cell. Mol. Life Sci.

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The localized control of second messenger levels sculpts dynamic and persistent changes in cell physiology and structure. Inositol trisphosphate [Ins(1,4,5)P(3)] 3-kinases (ITPKs) phosphorylate the intracellular second messenger Ins(1,4,5)P(3). These enzymes terminate the signal to release Ca(2+) from the endoplasmic reticulum and produce the messenger inositol tetrakisphosphate [Ins(1,3,4,5)P(4)]. Independent of their enzymatic activity, ITPKs regulate the microstructure of the actin cytoskeleton. The immune phenotypes of ITPK knockout mice raise new questions about how ITPKs control inositol phosphate lifetimes within spatial and temporal domains during lymphocyte maturation. The intense concentration of ITPK on actin inside the dendritic spines of pyramidal neurons suggests a role in signal integration and structural plasticity in the dendrite, and mice lacking neuronal ITPK exhibit memory deficits. Thus, the molecular and anatomical features of ITPKs allow them to regulate the spatiotemporal properties of intracellular signals, leading to the formation of persistent molecular memories.

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Section: Metabolism Of Inositol Trisphosphatementioning

confidence: 99%

Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling

Schell

2010

Cell. Mol. Life Sci.

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“…Calcium and magnesium ions had a slight negative effect on the L. chagasi enzyme activity and also modulated negatively the activity of serine peptidases from L. amazonensis promastigotes (Andrade et al 1998;Silva-López and Giovanni De Simone 2004a, b; Silva-López On the other hand, mammalian serine proteases, such as pancreatic trypsin and chymotrypsin, require calcium for their activity (Berezein and Martinek 1970). The difference between Leishmania serine peptidases and mammalian enzymes is paramount as calcium is an essential second messenger triggering intracellular responses in eukaryotic cells, activating phosphorylases and modulating the enzymatic activity (Shears 2009). In Leishmania, there are evidences that Ca 2+ participates in metaciclogenesis (Prasad et al 2001), adhesion to amastigotes in skin lesions (Goto et al 2008), apoptosis (Das et al 2008), infection signaling (Lanza et al 2004), as well as in Leishmania-macrophage binding (Misra et al 1991).…”

Section: Discussionmentioning

confidence: 99%

Serine protease activities in Leishmania (Leishmania) chagasi promastigotes

et al. 2010

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The present work reports the isolation, biochemical characterization, and subcellular location of serine proteases from aqueous, detergent soluble, and culture supernatant of Leishmania chagasi promastigote extracts, respectively, LCSII, LCSI, and LCSIII. The active enzyme molecular masses of LCSII were about 105, 66, and 60 kDa; of LCSI, 60 and 58 kDa; and of LCSIII, approximately 76 and 68 kDa. Optimal pH for the enzymes was 7.0 for LCSI and LCSIII and 8.5 for LCSII, and the optimal temperature for all enzymes was 37°C, using α-N-ρ-tosyl-L: -arginine methyl ester as substrate. Assay of thermal stability indicated that LCSIII is the more stable enzyme. Hemoglobin, bovine serum albumin, and ovalbumin were hydrolyzed by LCSII and LCSI but not by LCSIII. Inhibition studies suggested that enzymes belong to the serine protease class modulated by divalent cations. Rabbit antiserum against 56-kDa serine protease of Leishmania amazonensis identified proteins in all extracts of L. chagasi. Furthermore, immunocytochemistry demonstrated that serine proteases are located in flagellar pocket region and cytoplasmic vesicles of L. chagasi promastigotes. These findings indicate that L. chagasi serine proteases differ from L. amazonensis proteases and all known flagellate proteases, but display some similarities with serine proteases from other Leishmania species, suggesting a conservation of this enzymatic activity in the genus.

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“…InsP 4 is actually a group of several different isomers -3,4,5,6-InsP 4 , 1,4,5,6-InsP 4 , 1,3,4,5-InsP 4 and 1,3,4,6-InsP 4 -the first three of which have been shown to regulate chloride ion channels, histone acetylation and calcium signalling, respectively [3,81]. As anticipated by R. Irvine [52], these findings suggest that InsP 4 would fulfil relevant biological tasks, even if this evidence has still to be thoroughly assessed.…”

Section: Inositol Phosphatesmentioning

confidence: 99%

Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease

Bizzarri

Fuso

Dinicola

et al. 2016

Expert Opinion on Drug Metabolism & Toxicology

146

158

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Besides being a structural element, myo-inositol exerts unexpected functions, mostly unknown. However, several reports indicate that inositol plays a key role during phenotypic transitions and developmental phases. Furthermore, dysfunctions in the regulation of inositol metabolism have been implicated in several chronic diseases. Clinical trials using inositol in pharmacological doses provide amazing results in the management of gynecological diseases, respiratory stress syndrome, Alzheimer's disease, metabolic syndrome, and cancer, for which conventional treatments are disappointing. However, despite the widespread studies carried out to identify inositol-based effects, no comprehensive understanding of inositol-based mechanisms has been achieved. An integrated metabolomics-genomic study to identify the cellular fate of therapeutically administered myo-inositol and its genomic/enzymatic targets is urgently warranted.

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Molecular basis for the integration of inositol phosphate signaling pathways via human ITPK1

Cited by 21 publications

References 80 publications

Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling

Inositol trisphosphate 3-kinases: focus on immune and neuronal signaling

Serine protease activities in Leishmania (Leishmania) chagasi promastigotes

Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease

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