A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange
A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange
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DOI：
10.1073/pnas.93.22.12631
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发表时间：
1996-10-29
影响因子：
11.1
通讯作者：
Barber, DL
中科院分区：
文献类型：
--
作者：
Lin, X;Barber, DL
激活普遍表达的Na-H交换器NHE1导致细胞内H+外流增加，与这种H+外流相关的细胞内pH的增加可能有助于调节细胞的增殖、分化和肿瘤转化。虽然NHE1的活性是由生长因子和激素通过多个GTPase介导的途径来刺激的，但人们对NHE1是如何直接调控的知之甚少。通过表达文库筛选，我们发现了一个新的与NHE1特异结合的蛋白，该蛋白位于生长因子刺激交换活性的关键位置，该蛋白与钙调蛋白B和钙调蛋白同源，被命名为CHP。与NHE1一样，CHP在人体组织中广泛表达，CHP的瞬时过表达抑制了血清和GTP酶刺激的NHE1活性。CHP是一种磷酸化蛋白，CHP磷酸化状态可能是控制NHE1有丝分裂调控的重要信号。
Activation of the ubiquitously expressed Na-H exchanger, NHE1, results in an increased efflux of intracellular H+, The increase in intracellular pH associated with this H+ efflux may contribute to regulating cell proliferation, differentiation, and neoplastic transformation. Although NHE1 activity is stimulated by growth factors and hormones acting through multiple GTPase-mediated pathways, little is known about how the exchanger is directly regulated. Using expression library screening, we identified a novel protein that specifically binds to NHE1 at a site that is critical for growth factor stimulation of exchange activity, This protein is homologous to calcineurin B and calmodulin and is designated CHP for calcineurin B homologous protein, Like NHE1, CHP is widely expressed in human tissues, Transient overexpression of CHP inhibits serum- and GTPase stimulated NHE1 activity. CHP is a phosphoprotein and expression of constitutively activated GTPases decreases CHP phosphorylation, The phosphorylation state of CHP may therefore be an important signal controlling mitogenic regulation of NHE1.