ABCMdb

PMID: 23045527

Duan Y, Sun Y, Zhang F, Zhang WK, Wang D, Wang Y, Cao X, Hu W, Xie C, Cuppoletti J, Magin TM, Wang H, Wu Z, Li N, Huang P
Keratin K18 increases CFTR surface expression by binding to its C-terminal hydrophobic patch.
J Biol Chem. 2012 Oct 8., [PubMed]

Sentences

No. Mutations Sentence Comment

17 ABCC7 p.Ser1455* ABCC7 p.Gln1412* Interestingly, clinical studies suggest that the deletion of the CFTR C-terminal 26 residues by the S1455X mutation elevates the chloride concentration in sweat without producing any other CF symptoms, whereas the deletion of the C-terminal 69 residues by the Q1412X mutation results in severe CF (8-10). Login to comment 23 ABCC7 p.Ser1455* ABCC7 p.Gln1412* Interestingly, clinical studies suggest that the deletion of CFTR`s C-terminal 26 residues by the S1455X mutation elevates the chloride concentration in sweat without producing any other CF symptoms, while the deletion of the C-terminal 69 residues by Q1412X mutation results in severe CF (8-10). Login to comment 151 ABCC7 p.Tyr1424Ala Mutation of Tyr1424 to alanine did not alter CFTR-C-K18 binding, arguing against a role of AP2 in mediating the interaction between CFTR and K18. Login to comment 160 ABCC7 p.Tyr1424Ala ABCC7 p.Tyr1424Ala Mutation of Tyr1424 to alanine did not alter CFTR-C-K18 binding, arguing against a role of AP2 in mediating the interaction between CFTR and K18. Login to comment 238 ABCC7 p.Ser1455* ABCC7 p.Gln1412* It is possible that mutation Q1412X in CFTR, but not mutation S1455X, disrupts the K18 binding site and thus leads to the loss of plasmalemmal CFTR in epithelia and causes severe CF in patients. Login to comment 253 ABCC7 p.Tyr1424Ala In agreement with previous studies (4), substitution of Tyr1424 with an alanine in the CFTR C terminus (M4 mutation) strongly suppressed AP2-binding (Fig. 6A). Login to comment 291 ABCC7 p.Ser1455* ABCC7 p.Gln1412* It is possible that mutation Q1412X in CFTR, but not mutation S1455X, disrupts the K18-binding site and thus leads to the loss of plasmalemmal CFTR in epithelia and causes severe CF in patients. Login to comment 297 ABCC7 p.Tyr1424Ala Panel a, AP2 (top blot) and K18 (middle blot) from Calu-3 cells pulled down by GST alone (GST), GST-CFTR-(1407-1480) (WT), and GST-CFTR-(1407-1480) with 1413 FLVI1416 -AAAA (M1) or Y1424A (M4) mutations; the bottom blot shows loading of GST proteins. Login to comment