Decreased cyclin-dependent kinase activity promotes thyroid hormone-dependent tail regression in Rana catesbeiana.
The thyroid hormone (TH), 3,5,3'-triiodothyronine (T(3)), is an important regulator of diverse cellular processes including cell proliferation, differentiation, and apoptosis, with increasing evidence that the modulation of the phosphoproteome is an important factor in the TH-mediated response. However, little is understood regarding the mechanisms whereby phosphorylation may contribute to T(3)-mediated cellular outcomes during development. The cyclin-dependent kinases (Cdks) and mitogen-activated protein kinases (MAPK/ERK) have been implicated in TH signaling in mammalian cells. In this study, we have investigated, in frogs, the possible role that these kinases may have in the promotion of tail regression during tadpole metamorphosis, an important postembryonic process that is completely TH-dependent. Cdk2 steady state levels and activity increase in the tail concurrent with progression through the growth phase of metamorphosis, followed by a precipitous decrease coinciding with tail regression. Cyclin-A-associated kinase activity also follows a similar trend except that its associated kinase activity is maintained longer before a decrease in activity. Protein steady state levels of ERK1 and ERK2 remain relatively constant, and their kinase activities do not decrease until much later during tail regression. Tail tips cultured in serum-free medium in the presence of T(3) undergo regression, which is accelerated by coincubation with a specific Cdk2 inhibitor. Coincubation with PD098059, a MAPK inhibitor, has no effect. Thus, T(3)-dependent tail regression does not require MAPKs, but a decrease in Cdk2 activity promotes tail regression.
Skirrow
Rachel C
RC
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Helbing
Caren C
CC
D000818:Animals; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D007814:Larva / Q000187:drug effects; D008675:Metamorphosis, Biological / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011892:Rana catesbeiana / Q000502:physiology*; D013623:Tail / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D013963:Thyroid Hormones / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D013963:Thyroid Hormones; D051357:Cyclin-Dependent Kinase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3