RESUMEN
Peutz-Jeghers syndrome (PJS) is a very rare genetic disorder. PJS carries a high risk of developing gastrointestinal (GI) cancer or non-GI cancer with advancing years. However, major symptoms of PJS in childhood are obstruction, intussusception, and bleeding from hamartomatous intestinal polyps which in majority of cases are not related to cancer. Generally, first GI symptom develops by 20 years in one half of children diagnosed with PJS. Children under two years of age who had PJS polyp-related intestinal symptoms are rare, and there have been no published report on intestinal carcinoma development, adenomatous change or dysplasia of polyps in Korean children with PJS. Recently, the authors have experienced a case PJS with adenomatous polyp change in a 15-month-old boy who had STK11 gene mutation. Therefore, early evaluation could be necessary and considered in children with PJS.
Asunto(s)
Humanos , Lactante , Masculino , Adenoma/diagnóstico , Secuencia de Bases , Colonoscopía , Heterocigoto , Síndrome de Peutz-Jeghers/diagnóstico , Polimorfismo de Nucleótido Simple , Pólipos/patología , Proteínas Serina-Treonina Quinasas/químicaRESUMEN
WNKs (with-no-lysine [K]) are a family of serine-threonine protein kinases with an atypical placement of the catalytic lysine relative to all other protein kinases. The roles of WNK kinases in regulating ion transport were first revealed by the findings that mutations of two members cause a genetic hypertension and hyperkalemia syndrome. More recent studies suggest that WNKs are pleiotropic protein kinases with important roles in many cell processes in addition to ion transport. Here, we review roles of WNK kinases in the regulation of ion balance, cell signaling, survival, and proliferation, and embryonic organ development.
Asunto(s)
Animales , Humanos , Secuencia de Aminoácidos , Proliferación Celular , Supervivencia Celular , Hiperpotasemia/enzimología , Hipertensión/enzimología , Riñón/enzimología , Modelos Moleculares , Datos de Secuencia Molecular , Mutación , Neoplasias/enzimología , Estructura Terciaria de Proteína , Proteínas Serina-Treonina Quinasas/química , Seudohipoaldosteronismo/enzimología , Homología de Secuencia de Aminoácido , Transducción de Señal , SíndromeRESUMEN
Mechanism of regulation of eIF-2 alpha-subunit phosphorylation by dsI and p67 was studied. The results are as follows: (1) At low dsI concentration, p67 protected equimolar concentration of eIF-2. (2) At high dsI concentration, dsI efficiently phosphorylated eIF-2 alpha-subunit even when equimolar concentrations of both p67 and eIF-2 were present. Significantly increased p67 concentration was necessary to protect eIF-2 alpha-subunit at high dsI concentration. (3) dsI was also phosphorylated as it phosphorylated eIF-2 alpha-subunit. p67 inhibited both eIF-2 alpha-subunit and dsI phosphorylation similarly. (4) Although the [32P]-labelled dsI formed during the reaction could be effectively chased upon subsequent addition of excess unlabelled eIF-2 and ATP, the [32P] labelled eIF-2 formed under identical conditions, retained most of the radioactivity. (5) dsI coimmunoprecipitated with three subunit eIF-2 and p67 inhibited this coimmunoprecipitation reaction. It has been proposed: Three subunit eIF-2 and free p67 are in equilibrium with eIF-2 bound to p67 and, eIF-2.p67 complex is resistant to dsI phosphorylation. Activated dsI is already phosphorylated. At high concentration, dsI(P) can bind to free three subunit eIF-2 and form eIF-2.dsI(P) complex. dsI(P) in this complex then transfers its phosphoryl residue to eIF-2 and forms eIF-2 alpha(P) in an irreversible reaction. In a subsequent reaction, unphosphorylated dsI is autophosphorylated using [gamma 32P]-ATP and the cycle continues. Inhibition of eIF-2 alpha-subunit phosphorylation by p67 blocks this phosphorylation cycle and consequent dsI phosphorylation.