Phosphatidylinositol triphosphate kinase-dependent and c-jun NH2-terminal kinase-dependent induction of telomerase by calcium requires Pyk2.
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.
Alfonso-De Matte
Michelle Y
MY
Department of Pathology, University of South Florida and the H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA.
Kruk
Patricia A
PA
D000841:Anisomycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004492:Edetic Acid / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells; D005260:Female; D051418:Focal Adhesion Kinase 2; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D010051:Ovarian Neoplasms; D010053:Ovary / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D019098:Telomerase / Q000096:biosynthesis* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D002867:Chromones; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009025:Morpholines; D011994:Recombinant Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000841:Anisomycin; D004492:Edetic Acid; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019098:Telomerase; D002118:Calcium