Decreased cyclin-dependent kinase activity promotes thyroid hormone-dependent tail regression in <Emphasis Type="Italic">Rana catesbeiana</Emphasis> |
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Authors: | Rachel C Skirrow Caren C Helbing |
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Institution: | (1) Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055, Victoria, B.C., V8W 3P6, Canada |
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Abstract: | The thyroid hormone (TH), 3,5,3′-triiodothyronine (T3), 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 T3-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 T3 undergo regression, which is accelerated by coincubation with a specific Cdk2 inhibitor. Coincubation with PD098059, a MAPK
inhibitor, has no effect. Thus, T3-dependent tail regression does not require MAPKs, but a decrease in Cdk2 activity promotes tail regression.
This work was supported by a NSERC operating grant, NSERC University Faculty Award, and Michael Smith Foundationfor Health
Research Scholar Award. |
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Keywords: | Thyroid hormone Metamorphosis Cyclin-dependent kinase Protein phosphorylation North American bullfrog Rana catesbeiana (Anura) |
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