钙通过磷脂酰肌醇三磷酸激酶依赖性和c-jun氨基末端激酶依赖性诱导端粒酶需要Pyk2。

Phosphatidylinositol triphosphate kinase-dependent and c-jun NH2-terminal kinase-dependent induction of telomerase by calcium requires Pyk2.

作者信息

Alfonso-De Matte Michelle Y, Kruk Patricia A

机构信息

Department of Pathology, University of South Florida and the H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA.

出版信息

Cancer Res. 2004 Jan 1;64(1):23-6. doi: 10.1158/0008-5472.can-03-2820.

DOI:10.1158/0008-5472.can-03-2820

PMID:14729602

Abstract

Calcium signaling has been linked to activation of Pyk2, a calcium-dependent, focal adhesion kinase-related, non-receptor tyrosine kinase. Signaling via Pyk2 can activate c-jun NH(2)-terminal kinase (JNK). Calcium has also been shown to activate phosphatidylinositol triphosphate kinase and/or JNK. Here, we show that calcium signaling in ovarian surface epithelial cells not only induces telomerase activity via JNK but also activates Pyk2. Moreover, telomerase activation by Pyk2 requires JNK activation. In contrast, a kinase-deficient Pyk2 construct failed to activate either JNK or telomerase. Finally, we demonstrate that Pyk2 is capable of driving the human telomerase reverse transcriptase promoter, resulting in telomerase activation. These data suggest a novel role of Pyk2 for telomerase regulation.

摘要

钙信号传导与Pyk2的激活有关，Pyk2是一种钙依赖性、粘着斑激酶相关的非受体酪氨酸激酶。通过Pyk2的信号传导可激活c-jun氨基末端激酶（JNK）。钙也已被证明可激活磷脂酰肌醇三磷酸激酶和/或JNK。在此，我们表明卵巢表面上皮细胞中的钙信号传导不仅通过JNK诱导端粒酶活性，还激活Pyk2。此外，Pyk2介导的端粒酶激活需要JNK激活。相反，激酶缺陷型Pyk2构建体未能激活JNK或端粒酶。最后，我们证明Pyk2能够驱动人端粒酶逆转录酶启动子，从而导致端粒酶激活。这些数据表明Pyk2在端粒酶调节中具有新作用。