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首页> 外文期刊>American Journal of Physiology >Altered regulation of SHP-2 and PTP 1B tyrosine phosphatases in cystic kidneys from bcl-2 -/- mice.
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Altered regulation of SHP-2 and PTP 1B tyrosine phosphatases in cystic kidneys from bcl-2 -/- mice.

机译：bcl-2-/-小鼠胆囊肾脏中SHP-2和PTP 1B酪氨酸磷酸酶的调节改变。

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Protein tyrosine phosphorylation is a dynamic reversible process in which the level of phosphorylation, at any time, is the result of phosphatase and/or kinase activity. This balance is critical for control of growth and differentiation. The role of tyrosine phosphatases during nephrogenesis and in kidney disease requires delineation. Appropriate regulation of focal adhesion proteins such as focal adhesion kinase (FAK) and paxillin are important in cell adhesion, migration, and differentiation. We have previously shown that B cell lymphoma/leukemia-2 (bcl-2) -/- mice develop cystic kidneys and exhibit sustained phosphorylation of FAK and paxillin. We have examined the expression and activity of focal adhesion tyrosine phosphatases [Src homology-2 domain phosphatase (SHP-2), protein tyrosine phosphatase (PTP 1B), and PTP-proline, glutamate, serine, and threonine sequences (PEST)] during normal nephrogenesis and in cystic kidneys from bcl-2 -/- mice. Cystic kidneys from postnatal day 20 bcl-2 -/- mice demonstrate a reduced expression, sixfold decrease in activity, and altered distribution of SHP-2 and PTP 1B. PTP-PEST expression and distribution were similar in both bcl-2 +/+ and bcl-2 -/- mice. The altered regulation of PTP 1B and SHP-2 in kidneys from bcl-2 -/- mice correlates with sustained phosphorylation of FAK and paxillin. Thus renal cyst formation in the bcl-2 -/- mice may be the result of an inability of complete differentiation due to continued activation of growth processes, including activation of FAK and paxillin.
机译：蛋白质酪氨酸磷酸化是一个动态的可逆过程，其中磷酸化水平在任何时候都是磷酸酶和/或激酶活性的结果。这种平衡对于控制生长和分化至关重要。酪氨酸磷酸酶在肾生成过程中和在肾脏疾病中的作用需要描述。诸如粘着斑激酶（FAK）和paxillin等粘着斑蛋白的适当调节在细胞粘附，迁移和分化中很重要。先前我们已经证明B细胞淋巴瘤/白血病2（bcl-2）-/-小鼠会形成囊性肾脏，并表现出FAK和paxillin的持续磷酸化。我们检查了粘着斑酪氨酸磷酸酶[Src同源2域磷酸酶（SHP-2），蛋白酪氨酸磷酸酶（PTP 1B）和PTP脯氨酸，谷氨酸，丝氨酸和苏氨酸序列（PEST）的表达和活性。 bcl-2-/-小鼠的正常肾脏发生和囊性肾脏。出生后第20天的bcl-2-/-小鼠的囊性肾脏显示SHP-2和PTP 1B的表达降低，活性降低六倍以及分布改变。在bcl-2 + / +和bcl-2-/-小鼠中PTP-PEST的表达和分布相似。 bcl-2-/-小鼠肾脏中PTP 1B和SHP-2的调节改变与FAK和Paxillin的持续磷酸化有关。因此，bcl-2-/-小鼠中的肾囊肿形成可能是由于持续激活包括FAK和paxillin在内的生长过程而无法完全分化的结果。

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