{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:44:06Z","timestamp":1779345846838,"version":"3.51.4"},"reference-count":41,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,11,1]]},"abstract":"<jats:p>Phosphatidylinositol 4,5-bisphosphate (PIP2) activates KATP and other inward rectifier (Kir) channels. To determine residues important for PIP2 regulation, we have systematically mutated each positive charge in the COOH terminus of Kir6.2 to alanine. The effects of these mutations on channel function were examined using 86Rb efflux assays on intact cells and inside-out patch-clamp methods. Both methods identify essentially the same basic residues in two narrow regions (176\u2013222 and 301\u2013314) in the COOH terminus that are important for the maintenance of channel function and interaction with PIP2. Only one residue (R201A) simultaneously affected ATP and PIP2 sensitivity, which is consistent with the notion that these ligands, while functionally competitive, are unlikely to bind to identical sites. Strikingly, none of 13 basic residues in the terminal portion (residues 315\u2013390) of the COOH terminus affected channel function when neutralized. The data help to define the structural requirements for PIP2 sensitivity of KATP channels. Moreover, the regions and residues defined in this study parallel those uncovered in recent studies of PIP2 sensitivity in other inward rectifier channels, indicating a common structural basis for PIP2 regulation.<\/jats:p>","DOI":"10.1085\/jgp.116.5.599","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:50:20Z","timestamp":1027702220000},"page":"599-608","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":179,"title":["Structural Determinants of Pip2 Regulation of Inward Rectifier KATP Channels"],"prefix":"10.1085","volume":"116","author":[{"given":"Show-Ling","family":"Shyng","sequence":"first","affiliation":[{"name":"aCenter for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland, Oregon 97201"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine A.","family":"Cukras","sequence":"additional","affiliation":[{"name":"bDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Harwood","sequence":"additional","affiliation":[{"name":"aCenter for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland, Oregon 97201"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin G.","family":"Nichols","sequence":"additional","affiliation":[{"name":"bDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2000,10,16]]},"reference":[{"key":"2023072520285056700_Aguilar-Bryanetal1995","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1126\/science.7716547","article-title":"Cloning of the \u03b2-cell high affinity sulfonylurea receptora regulator of insulin secretion","volume":"268","author":"Aguilar-Bryan","year":"1995","journal-title":"Science."},{"key":"2023072520285056700_Ashcroft1998","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1146\/annurev.ne.11.030188.000525","article-title":"Adenosine 5\u2032-triphosphate-sensitive potassium channels","volume":"11","author":"Ashcroft","year":"1998","journal-title":"Annu. 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