DCI, D-Chiro-inositoli , myo-inositoli ja fytiini ( inositolihexafosfaatti)

https://D-chiro-inositol hexakisphosphate (D-chiro-IP6pmc.ncbi.nlm.nih.gov/articles/PMC12472782/

One emerging therapeutic avenue involves the modulation of insulin signaling, as insulin resistance is increasingly recognized as a central contributor to AD pathophysiology. Often referred to as “type 3 diabetes” [9], AD has been linked to impaired insulin signaling, which disrupts glucose metabolism, neuronal survival, and synaptic plasticity, thereby exacerbating neurodegeneration [6,9,10,11]. Insulin signaling in the central nervous system (CNS) is mediated through the phosphoinositide 3-kinase (PI3K)/AKT pathway, which is critical for energy homeostasis, neurotransmission, and synaptic integrity [12,13]. Defects in this pathway have been observed in AD patients and are associated with neuronal energy deficits, oxidative stress, and increased vulnerability to Aβ toxicity [12,13,14]. Furthermore, insulin resistance impacts glutamatergic neurotransmission, particularly through dysregulation of N-methyl-D-aspartate receptors (NMDARs), contributing to excitotoxicity, synaptic dysfunction and cognitive impairment [15,16,17].

In this context, insulin sensitizers such as D-chiro-inositol (DCI) represent a promising intervention for restoring insulin signaling in AD.

 DCI is a naturally occurring inositol isomer that can be incorporated into the body through diet and plays a crucial role in insulin-mediated glucose uptake and metabolism by acting through the PI3K/AKT pathway [18,19]. In addition to improving insulin sensitivity, DCI has been implicated in modulating neuroinflammatory responses and oxidative stress, which are key drivers of AD pathology [20,21,22]. Given its role in metabolic regulation, PI3K/AKT signaling [23], DCI may also influence glutamatergic signaling by stabilizing NMDAR function, potentially reducing excitotoxicity and synaptic deficits observed in AD. Preliminary observations indicate that DCI has beneficial effects in AD by counteracting the toxic actions of Abeta oligomers and by normalizing metabolic dysfunctions associated with amyloidosis in the humanized 5XFAD model of AD [24,2.....

. 2020 Apr 10;25(7):1720. doi: 10.3390/molecules25071720

New Frontiers for the Use of IP6 and Inositol Combination in Treating Diabetes Mellitus: A Review

Felix O Omoruyi ¹, Dewayne Stennett ², Shadae Foster ², Lowell Dilworth ^3,*

Editor: Ivana Vucenik

PMCID: PMC7212753  PMID: 32290029

. Inositol

Inositol is a saturated polyol with a six-carbon ring structure where each carbon is hydroxylated. They are isomers of hexahydroxy-cyclohexanes with nine possible geometrical forms, seven of which are optically inactive, and the remaining two form a chiral pair [10]. Some are biologically active, with the most common and most stable being myo-inositol [11,12]. Myo-inositol is water-soluble and found in a variety of food products [13]. Different safe doses of inositol have been reported in the literature. A daily oral dose of 18 g of inositol for three months has been reported to be safe and well-tolerated [14]. Others have suggested that myo-inositol is safe up to doses of 12 g per day [15]. Clements and Darnell [16] observed that the greatest amounts of myo-inositol were present in fruits, beans, grains, and nuts. Myo-inositol serves as the backbone and precursor of other inositol phosphates. It is produced in the human body from d-glucose and is present in all living cells as phosphatidylinositol and phytic acid [17]. It plays important physiological roles, which include mediation of osmoregulation, anticancer activity, and the enhancement of the anticancer effects of IP6 on various cancers [18,19,20]. It is also involved in the regulation of insulin release from the pancreatic beta-cells [21,22,23,24].

3. Myo-Inositol Hexakisphosphate

Myo-inositol hexakisphosphate (IP6), or phytic acid, is a natural organic phosphorus compound that is present in almost all plant and mammalian cells and is the phosphorus reservoir in all grains and oilseeds [25]. It is found in food sources high in fiber content, with the most abundant sources being wheat bran and flaxseed (0.4–6.4%) [26,27]. In most cereal crops, IP6 is the primary source of phosphorus. It possibly accounts for 65–85% of the total phosphorus in seeds, with the remaining phosphorus in the form of soluble inorganic phosphate and cellular phosphorus found in macromolecules such as nucleic acids, proteins, lipids and sugars [28,29].

The antinutrient nature of IP6 has been described in some studies [30,31]. However, emerging research shows that IP6, as well as the lower forms of inositol phosphates, IPs 2–5, may have essential physiological functions as well as anti-inflammatory and anticancer properties [32,33,34,35]. Recent studies have ascribed antioxidant and anti-diabetic properties to this group of compounds [36,37]. IP6 is produced within cells by de novo synthesis [38]. It is biosynthesized via two different routes, the lipid-dependent and lipid-independent pathways [39,40]. In plants, the lipid-dependent pathway is prominent in all plant organs, and the lipid-independent pathway is the more prominent of the two pathways in seeds only [41 d-glucose-6-phosphate is initially converted to myo-inositol 3-monophosphate by the enzyme myo-inositol 3-phosphate synthase. In the lipid-independent pathway, the myo-inositol 3-monophosphate undergoes a series of sequential phosphorylations through the action of various inositol phosphate kinases (Figure 1). For the lipid-dependent pathway, the myo-inositol 3-monophosphate is initially converted to myo-inositol, which is then converted to various phosphatidyl inositols, eventually leading to the formation of the higher inositol phosphates, IP5 and IP6 (Figure 1)

Fytiinin ja inositolin parhaat lähteet ovat  ekonomisesti edullisimmissa  ravintoaineissa, pavuissa, herneissä, pähkinöissä, manteleissa, viljan siemenissä, hedelmissä-

AXIS IRE1alfa-TRAF2-ASK1 ja mahdollisesti IRE1 beta.

 ERN1 eli IRE1beta

ASK1

https://pmc.ncbi.nlm.nih.gov/articles/PMC9038009/

Kesken

ENDOLYMFA, jonitasapainon säätelystä . Tärkeä kuuloaistin tarkkuudelle ja endogeenin taustahälyn vaimennukselle.

 https://pubmed.ncbi.nlm.nih.gov/35112133/

PubMed HAKU: Na+, K+, Cl-, ENDOLYMPHA.

•  2022 May;474(5):505-515.

doi: 10.1007/s00424-021-02661-9. Epub 2022 Feb 3. Low-salt diet increases mRNA expression of aldosterone-regulated transporters in the intermediate portion of the endolymphatic sac

Ai Matsubara ^{#  1} , Takenori Miyashita ^{#  2} , Kentaro Nakashima  ³ , Nozomu Mori  ² , Si-Young Song  ³ , Hiroshi Hoshikawa  ²

Affiliations

• PMID: 35112133
• DOI: 10.1007/s00424-021-02661-9

 Abstract

The endolymphatic sac is a small sac-shaped organ at the end of the membranous labyrinth of the inner ear. The endolymphatic sac absorbs the endolymph, in which the ion balance is crucial for inner ear homeostasis. Of the three sections of the endolymphatic sac, the intermediate portion is the center of endolymph absorption, particularly sodium transport, and is thought to be regulated by aldosterone. Disorders of the endolymphatic sac may cause an excess of endolymph (endolymphatic hydrops), a histological observation in Meniere’s disease. A low-salt diet is an effective treatment for Meniere’s disease, and is based on the assumption that the absorption of endolymph in the endolymphatic sac abates endolymphatic hydrops through a physiological increase in aldosterone level. However, the molecular basis of endolymph absorption in each portion of the endolymphatic sac is largely unknown because of difficulties in gene expression analysis, resulting from its small size and intricate structure. The present study combined reverse transcription-quantitative polymerase chain reaction and laser capture microdissection techniques to analyze the difference of gene expression of the aldosterone-controlled epithelial Na⁺ channel, thiazide-sensitive Na⁺-Cl⁻ cotransporter, and Na⁺, K⁺-ATPase genes in the three individual portions of the endolymphatic sac in a rat model. A low-salt diet increased the expression of aldosterone-controlled ion transporters, particularly in the intermediate portion of the endolymphatic sac. Our findings will contribute to the understanding of the physiological function of the endolymphatic sac and the pathophysiology of Meniere’s disease.

 

 

ENDOLYMPHA, glukoosi...PubMed haku , 30 artikkelia

HAKU PubMed: Endolympha, glucose

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1

Type 1 Diabetes Induces Hearing Loss: Functional and Histological Findings in An Akita Mouse Model.

Lee YY, Kim YJ, Gil ES, Kim H, Jang JH, Choung YH. Biomedicines. 2020 Sep 11;8(9):343. doi: 10.3390/biomedicines8090343. PMID: 32932780 Free PMC article.

The Akita mice had a significant increase in hearing thresholds, blood glucose, and insulin tolerance compared to WT mice. Histological analysis showed that the loss of cells and damage to mitochondria in the spiral ganglion neurons of Akita mice were significantly increas …

2

Localization of Glucose Transporter 10 to Hair Cells' Cuticular Plate in the Mouse Inner Ear.

Chen B, Wang Y, Geng M, Lin X, Tang W. Biomed Res Int. 2018 Jun 14;2018:7817453. doi: 10.1155/2018/7817453. eCollection 2018. PMID: 30013986 Free PMC article.

This study aimed to investigate the localization pattern of glucose transporters (Gluts) in mouse cochlea. Genome-wide gene expression analysis using CodeLink bioarrays indicated that Glut1 and Glut10 were highly expressed (~10-fold) in mouse cochlea compared with the othe …

3

Differential localizations of the myo-inositol transporters HMIT and SMIT1 in the cochlear stria vascularis.

Edamatsu M, Kondo Y, Ando M. Neurosci Lett. 2018 May 1;674:88-93. doi: 10.1016/j.neulet.2018.03.028. Epub 2018 Mar 15. PMID: 29551423

The cochlear stria vascularis produces endolymph and thereby plays an active role in inner ear homeostasis. We recently reported that the H(+)/myo-inositol cotransporter (HMIT) gene is expressed in the stria vascularis. ...

4

The gastric H,K-ATPase in stria vascularis contributes to pH regulation of cochlear endolymph but not to K secretion.

Miyazaki H, Wangemann P, Marcus DC. BMC Physiol. 2016 Aug 11;17(1):1. doi: 10.1186/s12899-016-0024-1. PMID: 27515813 Free PMC article.

The acid flux was decreased to about 40 % of control by removal of the metabolic substrate (glucose-free) and by inhibition of the sodium pump (ouabain). The flux was also decreased a) by inhibition of Na,H-exchangers by amiloride, dimethylamiloride (DMA), S3226 and Hoe694 …

5

Mitochondrial diabetes and deafness: possible dysfunction of strial marginal cells of the inner ear.

Olmos PR, Borzone GR, Olmos JP, Diez A, Santos JL, Serrano V, Cataldo LR, Anabalón JL, Correa CH. J Otolaryngol Head Neck Surg. 2011 Apr;40(2):93-103. PMID: 21453644 Review.

One of our MIDD patients inspired us to propose an integrated view on how a single mutation of the mitochondrial deoxyribonucleic acid (DNA) affects both the glucose metabolism and the inner ear physiology. DESIGN: (a) Study of mitochondrial DNA in a patient with MIDD. (b) …

6

Cellular localization of facilitated glucose transporter 1 (GLUT-1) in the cochlear stria vascularis: its possible contribution to the transcellular glucose pathway.

Ando M, Edamatsu M, Fukuizumi S, Takeuchi S. Cell Tissue Res. 2008 Mar;331(3):763-9. doi: 10.1007/s00441-007-0495-2. Epub 2008 Jan 15. PMID: 18196278

Immunoreactivity for the facilitated glucose transporter 1 (GLUT-1) has been found in the cochlear stria vascularis, but whether the strial marginal cells are immunopositive for GLUT-1 remains uncertain. ...The three-dimensional relationship between marginal cells and basa …

7

The multifaceted phenotype of the knockout mouse for the KCNE1 potassium channel gene.

Warth R, Barhanin J. Am J Physiol Regul Integr Comp Physiol. 2002 Mar;282(3):R639-48. doi: 10.1152/ajpregu.00649.2001. PMID: 11832382 Free article. Review.

Like patients, knockout mice are deaf and show vestibular symptoms due to an impaired endolymph production. Knockout mice show urinary and fecal salt wasting and volume depletion. The renal phenotype is due to diminished reabsorption of Na(+) and glucose. The mice a …

8

Effects of endolymphatic duct occlusion on the structure and function of the endolymphatic sac in the adult guinea pig.

Lee AJ, Parker DA, Gladstone HB, Hradek G, Schindler RA. Laryngoscope. 1995 Feb;105(2):192-7. doi: 10.1288/00005537-199502000-00016. PMID: 8544603

The present study was designed to determine the ELS response to slower changes in fluid dynamics by occluding the endolymphatic duct (ELD), thereby interrupting the longitudinal flow of endolymph to the ELS. Morphologic studies and autoradiographic techniques were used to …

9

Changes in hyaluronan synthesis by in vitro cultured endolymphatic sac cells.

Amoils CP, Schindler RA, Parker DA, Hradek GT. Am J Otol. 1992 Jul;13(4):343-6. PMID: 1415498

This model was chosen to determine whether a change in endolymph homeostasis affects ELS activity. Radiolabeled 14C glucose incorporation was used to evaluate HA synthesis by ELS cells when cultured in vitro. ...Therefore, the ELS cells of intact otocysts incorporat …

10

Hyaluronan synthesis by in vitro cultured endolymphatic sac cells.

Amoils CP, Schindler RA, Parker DA, Hradek GT. Am J Otol. 1992 Jul;13(4):303-7. PMID: 1415490

The ELS and portions of the membranous labyrinth were dissected from whole otocyst specimens and placed in 14C glucose-enhanced tissue culture media. A light microscopic (LM), autoradiographic study was performed to assess whether 14C glucose could be incorporated b …

ENDOLYMFA. Inositolin osuudesta osmoottisen miljöön säätelyssä

• 2018 May 1:674:88-93. doi: 10.1016/j.neulet.2018.03.028. Epub 2018 Mar 15.Differential localizations of the myo-inositol transporters HMIT and SMIT1 in the cochlear stria vascularis

Midori Edamatsu  ¹ , Yasuhiro Kondo  ² , Motonori Ando  ³

Affiliations

• PMID: 29551423
• DOI: 10.1016/j.neulet.2018.03.028

Abstract

The cochlear stria vascularis produces endolymph and thereby plays an active role in inner ear homeostasis. We recently reported that the H⁺/myo-inositol cotransporter (HMIT) gene is expressed in the stria vascularis. Here, we examined the protein localization of HMIT and Na⁺/myo-inositol cotransporter 1 (SMIT1) in the stria vascularis by immunohistochemistry. HMIT and SMIT1 were detected in the lateral wall of the cochlear duct. HMIT was widely detected throughout the stria vascularis, while SMIT1 was enriched in the strial basal cells. To examine the localization of HMIT in the stria vascularis in more detail, dissociated strial cells were immunostained, which resulted in the detection of HMIT immunoreactivity in marginal cells. These results indicate that HMIT is expressed in marginal cells and basal cells of the stria vascularis, while SMIT1 expression is enriched in basal cells. We speculate that HMIT and SMIT1 may play important roles in the homeostasis of cochlear fluids, for example by participating in pH regulation and osmoregulation.

Keywords: Endolymph; Inner ear; Osmoregulation; Rat (Brown Norway); pH. 

 

Genes: GeneCards

 HMIT, Alias SLC2A13 (12q12)

https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC2A13&keywords=HMIT 

Enables ATPase binding activity; myo-inositol:proton symporter activity; and protease binding activity. Involved in myo-inositol transport and positive regulation of amyloid-beta formation. Is integral component of plasma membrane. Part of cell body; cell periphery; and cell projection. [provided by Alliance of Genome Resources, Apr 2022]

SMIT1   (21q22.11)

 https://www.genecards.org/Search/Keyword?queryString=SMIT1

 Enables potassium channel regulator activity and transmembrane transporter binding activity. Predicted to be involved in inositol metabolic process; monosaccharide transmembrane transport; and myo-inositol import across plasma membrane. Predicted to act upstream of or within several processes, including peripheral nervous system development; positive regulation of reactive oxygen species biosynthetic process; and regulation of respiratory gaseous exchange. Located in plasma membrane. Part of perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Electrogenic Na(+)-coupled sugar symporter that actively transports myo-inositol and its stereoisomer scyllo-inositol across the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1 (By similarity). Maintains myo-inositol concentration gradient that defines cell volume and fluid balance during osmotic stress, in particular in the fetoplacental unit and central nervous system (By similarity). Forms coregulatory complexes with voltage-gated K(+) ion channels, allosterically altering ion selectivity, voltage dependence and gating kinetics of the channel. In turn, K(+) efflux through the channel forms a local electrical gradient that modulates electrogenic Na(+)-coupled myo-inositol influx through the transporter (PubMed:24595108, 28793216). Associates with KCNQ1-KCNE2 channel in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity) (PubMed:24595108). Associates with KCNQ2-KCNQ3 channel altering ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) permeation (PubMed:28793216). Provides myo-inositol precursor for biosynthesis of phosphoinositides such as PI(4,5)P2, thus indirectly affecting the activity of phosphoinositide-dependent ion channels and Ca(2+) signaling upon osmotic stress (PubMed:27217553). ( SC5A3_HUMAN,P53794 )

KCNQ1-KCNE2 channel KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability (By similarity). ( KCNE2_HUMAN,Q9Y6J6 )

 

UniProtKB/Swiss-Prot Summary for KCNQ1 Gene (11p15.5-p15.4), 

Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (PubMed:10646604, 25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:10646604, 11101505, 19687231, 8900283, 9108097, 9312006). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:10646604, 11101505, 25441029, 8900283, 9108097, 9312006). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:10646604, 11101505, 8900283, 9108097, 9312006). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568). KCNQ1-KCNE2 channel associates with Na(+)-coupled myo-inositol symporter in the apical membrane of choroid plexus epithelium and regulates the myo-inositol gradient between blood and cerebrospinal fluid with an impact on neuron excitability. ( KCNQ1_HUMAN,P51787 )

  Interacts with KCNE2; forms a heterooligomer complex that targets to the membrane raft and leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505, 20533308).   ->  KCNE2 (Gene 21q22.11) 

 HAIR CELLS

https://pubmed.ncbi.nlm.nih.gov/34566562/

JONITASAPAINOSTA ENDOLYM;FASSA

ENDOLYMFA. Sisäkorvan homeostaattisista järjestelmistä

 ENDOLYMFASTA : Sisäkorvan  miljööstä.

• 2001;7(2):72-83.Blood-labyrinth barrier and fluid dynamics of the inner ear

S K Juhn  ¹ , B A Hunter, R M Odland

Affiliations PMID: 14689642

Abstract

Under normal conditions, the inner ear possesses remarkably stable homeostatic mechanisms for the maintenance of functional integrity of the inner ear fluid. The inner ear fluid maintains its homeostasis by a variety of regulatory mechanisms such as an ion transport system, a blood-labyrinth barrier, and a constant blood supply. Highly regulated transport of ions into and out of the inner ear provides for the maintenance of inner ear fluid composition necessary for auditory transduction. Any disturbance in one of these mechanisms can disrupt homeostasis expressed by ionic, osmotic, or metabolic imbalance between the compartments. Free radicals, stress hormones, noise exposure, and aminoglycoside antibiotics may induce short- and long-term effects on cellular function of the auditory or vestibular system (or both) and serve as a triggering mechanism for abrupt functional disturbances of inner ear fluid ion homeostasis. In this article, we present a comprehensive review of the mechanisms underlying inner ear fluid homeostasis necessary for normal auditory function and factors that can disrupt homeostasis and lead to functional disturbances, namely sensorineural hearing loss, tinnitus, and vertigo.

MIKÄ ON INOSITOLIN OSUUS ENDOLYMFAMILJÖÖN HOMEOSTAASISSA?  Katso seuraava artikkeli.Endolymfa ja osmoottinen stressi. Inositolilla  funktiota .

PIK3CA ( asian musta aukko: inositoli , inositolifosfaatti, fosfatidyyli-inositoli - tämän kohdan normaali metabolinen kartta)

 

Aliases for PIK3CA Gene

• GeneCards Symbol: PIK3CA ²
• Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha ^{2 3 5}
• PI3K ^{2 3 5}
• Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Isoform ^{3 4}
• Phosphoinositide-3-Kinase, Catalytic, Alpha Polypeptide ^{2 3}
• Serine/Threonine Protein Kinase PIK3CA ^{3 4}
• PtdIns-3-Kinase Subunit P110-Alpha ^{3 4}
• Phosphoinositide 3-Kinase Alpha ^{3 4}
• PI3K-Alpha ^{3 4}
• Phosphatidylinositol-4,5-Bisphosphate 3-Kinase 110 KDa Catalytic Subunit Alpha ³
• Phosphatidylinositol 4,5-Bisphosphate 3-Kinase 110 KDa Catalytic Subunit Alpha ⁴
• Mutant Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha ³
• Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha ²
• Phosphatidylinositol 3-Kinase, Catalytic, Alpha Polypeptide ³
• Phosphatidylinositol 3-Kinase, Catalytic, 110-KD, Alpha ³
• Phosphoinositide-3-Kinase Catalytic Alpha Polypeptide ⁴
• PI3-Kinase P110 Subunit Alpha ³

• PtdIns-3-Kinase Subunit Alpha ⁴
• PI3-Kinase Subunit Alpha ⁴
• EC 2.7.1.137 ⁴
• EC 2.7.1.153 ⁴
• EC 2.7.11.1 ⁴
• P110-Alpha ³
• PI3Kalpha ⁴
• P110alpha ⁴
• EC 2.7.1 ⁴⁸
• CLAPO ³
• CLOVE ³
• MCMTC ³
• CCM4 ³
• CWS5 ³
• MCAP ³
• MCM ³

External Ids for PIK3CA Gene

• HGNC: 8975
• NCBI Gene: 5290
• Ensembl: ENSG00000121879
• OMIM®: 171834
• UniProtKB/Swiss-Prot: P42336

NCBI Gene Summary for PIK3CA Gene

• Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]

CIViC Summary for PIK3CA Gene

• PIK3CA is the most recurrently mutated gene in breast cancer, and has been found to important in a number of cancer types. An integral part of the PI3K pathway, PIK3CA has long been described as an oncogene, with two main hotspots for activating mutations, the 542/545 region of the helical domain, and the 1047 region of the kinase domain. PIK3CA, and its interaction with the AKT and mTOR pathways, is the subject of an immense amount of research and development, and PI3K inhibition has seen some limited success in recent clinical trials. While monotherapies seem to be limited in their potential, there is a recent interest in pursuing PI3K inhibition as part of a combination therapy regiment with inhibition partners including TKI's, MEK inhibitors, PARP inhibitors, and in breast cancer, aromatase inhibitors.

GeneCards Summary for PIK3CA Gene

PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) is a Protein Coding gene. Diseases associated with PIK3CA include Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome and Congenital Lipomatous Overgrowth, Vascular Malformations, And Epidermal Nevi. Among its related pathways are Downstream signaling of activated FGFR2 and Translation Insulin regulation of translation. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein serine/threonine kinase activity. An important paralog of this gene is PIK3CB.

UniProtKB/Swiss-Prot Summary for PIK3CA Gene

Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides (PubMed:15135396, 23936502, 28676499). Uses ATP and PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:15135396, 28676499). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to various growth factors. Involved in the activation of AKT1 upon stimulation by receptor tyrosine kinases ligands such as EGF, insulin, IGF1, VEGFA and PDGF. Involved in signaling via insulin-receptor substrate (IRS) proteins. Essential in endothelial cell migration during vascular development through VEGFA signaling, possibly by regulating RhoA activity. Required for lymphatic vasculature development, possibly by binding to RAS and by activation by EGF and FGF2, but not by PDGF. Regulates invadopodia formation through the PDPK1-AKT1 pathway. Participates in cardiomyogenesis in embryonic stem cells through a AKT1 pathway. Participates in vasculogenesis in embryonic stem cells through PDK1 and protein kinase C pathway. In addition to its lipid kinase activity, it displays a serine-protein kinase activity that results in the autophosphorylation of the p85alpha regulatory subunit as well as phosphorylation of other proteins such as 4EBP1, H-Ras, the IL-3 beta c receptor and possibly others (PubMed:23936502, 28676499). Plays a role in the positive regulation of phagocytosis and pinocytosis (By similarity). ( PK3CA_HUMAN,P42336 )

Tocris Summary for PIK3CA Gene

• PI 3-Kinases (phosphoinositide 3-kinases, PI 3-Ks) are a family of lipid kinases capable of phosphorylating the 3'OH of the inositol ring of phosphoinositides. They are responsible for coordinating a diverse range of cell functions including proliferation and survival.

Gene Wiki entry for PIK3CA Gene

Cytogenetic band:

• 3q26.32 by HGNC
• 3q26.32 by NCBI Gene
• 3q26.32 by Ensembl
•  

Protein Symbol:

P42336-PK3CA_HUMAN

Recommended name:

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform

Protein attributes for PIK3CA Gene

Size:

1068 amino acids

Molecular mass:

124284 Da

Protein existence level:

PE1

Quaternary structure:

• Heterodimer of a catalytic subunit PIK3CA and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3) (PubMed:26593112).
  Interacts with IRS1 in nuclear extracts (By similarity).
  Interacts with RUFY3 (By similarity).
  Interacts with RASD2 (By similarity).
  Interacts with APPL1.
  Interacts with HRAS and KRAS (By similarity).
  Interaction with HRAS/KRAS is required for PI3K pathway signaling and cell proliferation stimulated by EGF and FGF2 (By similarity).
  Interacts with FAM83B; activates the PI3K/AKT signaling cascade (PubMed:23676467).

Miscellaneous:

• The avian sarcoma virus 16 genome encodes an oncogene derived from PIK3CA.

 

Molecular function for PIK3CA Gene according to UniProtKB/Swiss-Prot KTS- gene cards lähteestä jatkoteksti: https://www.genecards.org/cgi-bin/carddisp.pl?gene=PIK3CA&keywords=PIK3CA