IndraLab
Statements
reach
"XREF_BIBR, XREF_BIBR, XREF_BIBR In the case of LQT11, a mutation within AKAP9, which encodes an A kinase anchoring protein responsible for facilitating phosphorylation of KCNQ1 by protein kinase A, impairs I Ks augmentation, leading to a clinical phenotype similar to that for LQT1 and LQT5."
reach
"17-B estradiol (E2) inhibits Cl - secretion via PKC and PKA dependent phosphorylation of the KCNQ1 : KCNE3 K + channels in colonic crypts and berberine displays a remarkably similar mechanism of antisecretory action to E2 (both inhibit KCNQ1 channels by protein kinase phosphorylation and neither molecule inhibits CFTR)."
sparser
"β1-AR activation leads to activation of protein kinase A (PKA), which directly phosphorylates the KCNQ1 subunit, increasing I Ks function. xref - xref The increase in I Ks is thought to suppress the premature beats and afterdepolarization induced by increased L-type Ca 2+ currents during β-adrenergic stimulation. xref Accordingly, ß-blockers have been considered the first-line therapy in LQT1 patients without a history of aborted cardiac arrest (ACA)."
sparser
"For example, loss-of-function mutations in the pore-forming α‑subunit Kv7.1, β‑subunit KCNE1 and the AKAP Yotiao have been identified that disrupt the I Ks macromolecular complex and thereby prevent PKA-dependent phosphorylation of Kv7.1 and subsequent upregulation of I Ks during sympathetic stimulation [ xref , xref ]."
sparser
"Specifically, recent findings from Kass and Ackerman have identified AKAP9-S1570L which markedly diminishes the interaction of yotiao with KCNQ1, resulting in reduction in PKA-dependent phosphorylation of Kv7.1, and thus striking inhibition of I KS regulation by cAMP. xref Similar to models of LQT1 - associated mutations in KCNQ1 that block yotiao binding and I KS phospho-regulation, yotiao mutations are also predicted to prolong the action potential and increase arrhythmia susceptibility (now termed type 11 long QT syndrome). xref In support of this notion, the S1570L proband displayed a clinical LQTS phenotypes (now referred to as type 11 long QT syndrome; MIM#611820) similar to LQT1 mutations that block KCNQ1 association with yotiao (female, QT c 485 ms presenting with syncope and family history of LQTS). xref Together, these two related studies have revealed the critical importance of local regulation of ion channels by accessory ChIPs, as well as demonstrate the power of combining clinical genetics and molecular/cellular cardiology to drive disease discovery."