Molecular Cloning and Functional Expression of the K-Cl Cotransporter from Rabbit, Rat, and Human

Gillen, Christopher M.; Brill, Susan; Payne, John A.; Forbush, Bliss

doi:10.1074/jbc.271.27.16237

Cited by 345 publications

(365 citation statements)

References 51 publications

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“…1A shows that 50 ng/ml IGF-1 increased swelling-activated K ϩ ( 86 Rb ϩ ) efflux in a time-dependent manner, when measured in Cl Ϫ -containing medium. In contrast, swelling-activated K ϩ ( 86 Rb ϩ ) was independent of IGF-1 stimulation when NO 3 Ϫ was substituted for Cl Ϫ in the efflux medium. KCC activity is taken as the Cl Ϫ -dependent K ϩ ( 86 Rb ϩ ) flux, defined as the difference between efflux into Cl Ϫ and NO 3 Ϫ media.…”

Section: Igf-1 Stimulated Kcc Activity and Enhanced Kcc-dependent Cellmentioning

confidence: 89%

“…86 Rb ϩ efflux rate constants were estimated from the negative slope of the graph of ln[X i (t)/X i (t ϭ 0)] versus time (t), where X i (t ϭ 0) denotes the total amount of 86 Rb ϩ inside the cells at the beginning of the efflux time course and X i (t) denotes the amount of 86 Rb ϩ inside the cells at the time point t. To study the KCC activity, the Cl Ϫ dependence of K ϩ ( 86 Rb ϩ ) efflux was examined by substituting NO 3 Ϫ for Cl Ϫ in the efflux medium. The Cl Ϫ -dependent K ϩ ( 86 Rb ϩ ) flux was defined as the efflux difference between Cl Ϫ and NO 3 Ϫ media. Measurements of Cell Volume-Cell volume was measured at 37°C as described previously (9,13).…”

Section: Cell Cultures and Creation Of Kcc Mutant Cell Lines-mentioning

confidence: 99%

“…KCC activity is taken as the Cl Ϫ -dependent K ϩ ( 86 Rb ϩ ) flux, defined as the difference between efflux into Cl Ϫ and NO 3 Ϫ media. However, in the presence of the KCC inhibitor DIOA (50 M), the swelling-activated K ϩ ( 86 Rb ϩ ) efflux was insensitive to IGF-1 stimulation whether efflux was measured in Cl Ϫ -or NO 3 Ϫ -containing medium (Fig. 1B).…”

Section: Igf-1 Stimulated Kcc Activity and Enhanced Kcc-dependent Cellmentioning

confidence: 99%

“…The cDNA products of four KCC genes have been cloned. The activities of KCC1, KCC3, and KCC4 are osmotically sensitive and involved in cell volume regulation (3)(4)(5). The neuron-specific KCC2 is critical for the maturation of inhibitory GABA responses in the central nervous system by the control of intracellular Cl Ϫ concentration (6).…”

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confidence: 99%

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Insulin-like Growth Factor 1 Stimulates KCl Cotransport, Which Is Necessary for Invasion and Proliferation of Cervical Cancer and Ovarian Cancer Cells

Shen¹,

Lin²,

Hsu³

et al. 2004

Journal of Biological Chemistry

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The mechanisms by which insulin-like growth factor 1 (IGF-1) cooperates with membrane ion transport system to modulate epithelial cell motility and proliferation remain poorly understood. Here, we investigated the role of electroneutral KCl cotransport (KCC), in IGF-1-dependent invasiveness and proliferation of cervical and ovarian cancer cells. IGF-1 increased KCC activity and mRNA expression in a dose-and time-dependent manner in parallel with the enhancement of regulatory volume decrease. IGF-1 treatment triggers phosphatidylinositol 3-kinase and mitogen-activated protein kinase cascades leading to the activation of Akt and extracellular signal-regulated kinase1/2 (Erk1/2), respectively. The activated Erk1/2 mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways are differentially required for IGF-1-stimulated biosynthesis of KCC polypeptides. Specific reduction of Erk1/2 protein levels with small interference RNA abolishes IGF-1-stimulated KCC activity. Pharmacological inhibition and genetic modification of KCC activity demonstrate that KCC is necessary for IGF-1-induced cancer cell invasiveness and proliferation. IGF-1 and KCC colocalize in the surgical specimens of cervical cancer (n ‫؍‬ 28) and ovarian cancer (n ‫؍‬ 35), suggesting autocrine or paracrine IGF-1 stimulation of KCC production. Taken together, our results indicate that KCC activation by IGF-1 plays an important role in IGF-1 signaling to promote growth and spread of gynecological cancers.

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Section: Igf-1 Stimulated Kcc Activity and Enhanced Kcc-dependent Cellmentioning

confidence: 89%

Section: Cell Cultures and Creation Of Kcc Mutant Cell Lines-mentioning

confidence: 99%

Section: Igf-1 Stimulated Kcc Activity and Enhanced Kcc-dependent Cellmentioning

confidence: 99%

mentioning

confidence: 99%

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Insulin-like Growth Factor 1 Stimulates KCl Cotransport, Which Is Necessary for Invasion and Proliferation of Cervical Cancer and Ovarian Cancer Cells

Shen¹,

Lin²,

Hsu³

et al. 2004

Journal of Biological Chemistry

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“…1 the basolateral or secretory isoform of the Na-K2Cl cotransporter (1,2), is a member of the cation-coupled chloride transporter family (3,4), which includes the apical Na-K-2Cl cotransporter of the renal thick ascending limb (5,6), the NaCl cotransporter of the renal distal convoluted tubule (6), and four KCl cotransporters (7)(8)(9). NKCC1 mediates the coupled electroneutral transport of 1 Na ϩ , 1 K ϩ , and 2 Cl Ϫ ions across the plasma membrane (4), driven by the inwardly directed Na ϩ and Cl Ϫ gradients that occur under physiological conditions.…”

Section: Nkcc1mentioning

confidence: 99%

Mice Lacking the Basolateral Na-K-2Cl Cotransporter Have Impaired Epithelial Chloride Secretion and Are Profoundly Deaf

Flagella¹,

Clarke²,

Miller³

et al. 1999

Journal of Biological Chemistry

358

349

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In chloride-secretory epithelia, the basolateral Na-K2Cl cotransporter (NKCC1) is thought to play a major role in transepithelial Cl ؊ and fluid transport. Similarly, in marginal cells of the inner ear, NKCC1 has been proposed as a component of the entry pathway for K ؉ that is secreted into the endolymph, thus playing a critical role in hearing. To test these hypotheses, we generated and analyzed an NKCC1-deficient mouse. Homozygous mutant (Nkcc1 ؊/؊ ) mice exhibited growth retardation, a 28% incidence of death around the time of weaning, and mild difficulties in maintaining their balance. Mean arterial blood pressure was significantly reduced in both heterozygous and homozygous mutants, indicating an important function for NKCC1 in the maintenance of blood pressure. cAMP-induced short circuit currents, which are dependent on the CFTR Cl ؊ channel, were reduced in jejunum, cecum, and trachea of Nkcc1 ؊/؊ mice, indicating that NKCC1 contributes to cAMP-induced Cl ؊ secretion. In contrast, secretion of gastric acid in adult Nkcc1 ؊/؊ stomachs and enterotoxin-stimulated fluid secretion in the intestine of suckling Nkcc1 ؊/؊ mice were normal. Finally, homozygous mutants were deaf, and histological analysis of the inner ear revealed a collapse of the membranous labyrinth, consistent with a critical role for NKCC1 in transepithelial K ؉ movements involved in generation of the K ؉ -rich endolymph and the endocochlear potential.

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Electrolyte Secretion and Absorption in the Small Intestine and Colon

Barrett

Keely

2015

Yamada' S Textbook of Gastroenterology

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Molecular Cloning and Functional Expression of the K-Cl Cotransporter from Rabbit, Rat, and Human

Cited by 345 publications

References 51 publications

Insulin-like Growth Factor 1 Stimulates KCl Cotransport, Which Is Necessary for Invasion and Proliferation of Cervical Cancer and Ovarian Cancer Cells

Insulin-like Growth Factor 1 Stimulates KCl Cotransport, Which Is Necessary for Invasion and Proliferation of Cervical Cancer and Ovarian Cancer Cells

Mice Lacking the Basolateral Na-K-2Cl Cotransporter Have Impaired Epithelial Chloride Secretion and Are Profoundly Deaf

Electrolyte Secretion and Absorption in the Small Intestine and Colon

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