Novel Functional Features of cGMP Substrate Proteins IRAG1 and IRAG2
The inositol triphosphate-associated proteins IRAG1 and IRAG2 are cGMP kinase substrate proteins that regulate intracellular Ca<sup>2+</sup>. Previously, IRAG1 was discovered as a 125 kDa membrane protein at the endoplasmic reticulum, which is associated with the intracellular Ca<sup&...
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MDPI AG
2023-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/12/9837 |
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| author | Sally Prüschenk Michael Majer Jens Schlossmann |
| author_facet | Sally Prüschenk Michael Majer Jens Schlossmann |
| author_sort | Sally Prüschenk |
| collection | DOAJ |
| description | The inositol triphosphate-associated proteins IRAG1 and IRAG2 are cGMP kinase substrate proteins that regulate intracellular Ca<sup>2+</sup>. Previously, IRAG1 was discovered as a 125 kDa membrane protein at the endoplasmic reticulum, which is associated with the intracellular Ca<sup>2+</sup> channel IP<sub>3</sub>R-I and the PKGIβ and inhibits IP<sub>3</sub>R-I upon PKGIβ-mediated phosphorylation. IRAG2 is a 75 kDa membrane protein homolog of IRAG1 and was recently also determined as a PKGI substrate. Several (patho-)physiological functions of IRAG1 and IRAG2 were meanwhile elucidated in a variety of human and murine tissues, e.g., of IRAG1 in various smooth muscles, heart, platelets, and other blood cells, of IRAG2 in the pancreas, heart, platelets, and taste cells. Hence, lack of IRAG1 or IRAG2 leads to diverse phenotypes in these organs, e.g., smooth muscle and platelet disorders or secretory deficiency, respectively. This review aims to highlight the recent research regarding these two regulatory proteins to envision their molecular and (patho-)physiological tasks and to unravel their functional interplay as possible (patho-)physiological counterparts. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T02:22:20Z |
| publishDate | 2023-06-01 |
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| spelling | doaj.art-378a4f1721db447e8752cb829484975e2023-11-18T10:44:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-012412983710.3390/ijms24129837Novel Functional Features of cGMP Substrate Proteins IRAG1 and IRAG2Sally Prüschenk0Michael Majer1Jens Schlossmann2Department of Pharmacology and Toxicology, Institute of Pharmacy, University of Regensburg, 93040 Regensburg, GermanyDepartment of Pharmacology and Toxicology, Institute of Pharmacy, University of Regensburg, 93040 Regensburg, GermanyDepartment of Pharmacology and Toxicology, Institute of Pharmacy, University of Regensburg, 93040 Regensburg, GermanyThe inositol triphosphate-associated proteins IRAG1 and IRAG2 are cGMP kinase substrate proteins that regulate intracellular Ca<sup>2+</sup>. Previously, IRAG1 was discovered as a 125 kDa membrane protein at the endoplasmic reticulum, which is associated with the intracellular Ca<sup>2+</sup> channel IP<sub>3</sub>R-I and the PKGIβ and inhibits IP<sub>3</sub>R-I upon PKGIβ-mediated phosphorylation. IRAG2 is a 75 kDa membrane protein homolog of IRAG1 and was recently also determined as a PKGI substrate. Several (patho-)physiological functions of IRAG1 and IRAG2 were meanwhile elucidated in a variety of human and murine tissues, e.g., of IRAG1 in various smooth muscles, heart, platelets, and other blood cells, of IRAG2 in the pancreas, heart, platelets, and taste cells. Hence, lack of IRAG1 or IRAG2 leads to diverse phenotypes in these organs, e.g., smooth muscle and platelet disorders or secretory deficiency, respectively. This review aims to highlight the recent research regarding these two regulatory proteins to envision their molecular and (patho-)physiological tasks and to unravel their functional interplay as possible (patho-)physiological counterparts.https://www.mdpi.com/1422-0067/24/12/9837cGMPcGKIIP<sub>3</sub>R-IIP<sub>3</sub>R-IIIP<sub>3</sub>R-IIIIRAG |
| spellingShingle | Sally Prüschenk Michael Majer Jens Schlossmann Novel Functional Features of cGMP Substrate Proteins IRAG1 and IRAG2 International Journal of Molecular Sciences cGMP cGKI IP<sub>3</sub>R-I IP<sub>3</sub>R-II IP<sub>3</sub>R-III IRAG |
| title | Novel Functional Features of cGMP Substrate Proteins IRAG1 and IRAG2 |
| title_full | Novel Functional Features of cGMP Substrate Proteins IRAG1 and IRAG2 |
| title_fullStr | Novel Functional Features of cGMP Substrate Proteins IRAG1 and IRAG2 |
| title_full_unstemmed | Novel Functional Features of cGMP Substrate Proteins IRAG1 and IRAG2 |
| title_short | Novel Functional Features of cGMP Substrate Proteins IRAG1 and IRAG2 |
| title_sort | novel functional features of cgmp substrate proteins irag1 and irag2 |
| topic | cGMP cGKI IP<sub>3</sub>R-I IP<sub>3</sub>R-II IP<sub>3</sub>R-III IRAG |
| url | https://www.mdpi.com/1422-0067/24/12/9837 |
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