RESUMO
G protein-coupled receptor kinase 2 (GRK2) emerges as a key modulator of G protein-coupled receptors and other plasma membrane receptors triggered by chemotactic messengers. In addition, GRK2 has been reported to interact with a variety of signal transduction proteins related to cell migration. Interestingly, the levels of expression and activity of this kinase are altered in several inflammatory disorders, thus suggesting that it may play an important role in the onset or progression of these pathologies. This review summarizes the mechanisms involved in the control of GRK2 expression and function and highlights novel functional interactions of this protein that might help to explain how altered GRK2 levels affects cell migration in different cell types and pathological settings (AU)
La quinasa GRK2 (G protein-coupled receptor kinase 2) se perfila como un modulador clave de receptores acoplados a proteínas G y de otros receptores de membrana plasmática que responden a estímulos migratorios. Además, GRK2 es capaz de interaccionar con diferentes proteínas señalizadoras relacionadas con la migración celular. Por otra parte, puesto que los niveles de expresión y actividad de esta quinasa se encuentran alterados en distintas en enfermedades inflamatorias, se sugiere que GRK2 puede desempeñar un papel importante en el desencadenamiento o la progresión de estos procesos. Esta revisión resume los mecanismos implicados en el control de la expresión y función de GRK2 y resalta nuevas interacciones funcionales de esta proteína que pueden contribuir a explicar cómo las alteraciones en los niveles de GRK2 afectan a la migración de distintos tipos celulares y a diversas situaciones patológicas (AU)
Assuntos
Animais , Camundongos , Protamina Quinase/administração & dosagem , Protamina Quinase/síntese química , Inflamação/complicações , Inflamação/diagnóstico , Membrana Celular/metabolismo , Artrite/diagnóstico , Linfonodos/anormalidades , Protamina Quinase/farmacologia , Protamina Quinase , Inflamação/metabolismo , Inflamação/prevenção & controle , Membrana Celular/enzimologia , Artrite/enzimologia , Linfonodos/lesõesRESUMO
The requirement of protein kinase C zeta (zeta PKC) for maturation of X. laevis oocytes in response to insulin, p21ras, and phosphatidylcholine-hydrolyzing phospholipase C has recently been shown. Here we present experimental evidence demonstrating that activation of zeta PKC is not only necessary but also sufficient by itself to activate maturation in oocytes and to produce deregulation of growth control in mouse fibroblasts. Furthermore, by using a dominant kinase-defective mutant of zeta PKC, we confirm that this kinase is required for mitogenic activation in oocytes and fibroblasts. These results permit us to propose zeta PKC as a critical step downstream of p21ras in mitogenic signal transduction.
Assuntos
Isoenzimas/metabolismo , Oócitos/fisiologia , Proteína Quinase C/metabolismo , Transdução de Sinais , Células 3T3 , Sequência de Aminoácidos , Animais , Bacillus cereus/enzimologia , Sequência de Bases , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Replicação do DNA/efeitos dos fármacos , Feminino , Vetores Genéticos , Substâncias de Crescimento/farmacologia , Insulina/farmacologia , Isoenzimas/genética , Camundongos , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos , Oócitos/citologia , Oócitos/efeitos dos fármacos , Fosforilação , Plasmídeos , Protamina Quinase/farmacologia , Proteína Quinase C/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , RNA/genética , RNA/metabolismo , Transfecção , Fosfolipases Tipo C/isolamento & purificação , Fosfolipases Tipo C/farmacologia , Xenopus laevisRESUMO
By injecting heterologous histone-kinase preparations into ovarian Axolotl oocytes, it has been possible to speed up the progesterone-induced process of chromosome condensation. Moreover, in some instances, this condensation and even complete maturation have been obtained after injection of protein kinase alone, thus in the absence of hormone stimulation. Two different histone kinase preparations have been used: one was prepared from ascites cell chromatin and the other from in vitro ovulated Xenopus oocytes.
