title: Replication checkpoint control by a PTK/STAT3/cyclin D1 axis.
abstract: Tyrosine phosphorylation-dependent signalling, controlled by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), is typically associated with the cellular response to mitogens in G1. However, a growing number of studies indicate that PTKs and PTPs can have important roles in cellular division beyond this initial phase of the cell cycle. In this Perspective we discuss the impact and contributions of PTKs and PTPs to cell cycle checkpoints. We focus on the replication checkpoint and our recent findings that demonstrate that the attenuation of PTK-mediated STAT3 signalling for the depletion of cyclin D1, works in concert with ATR-instigated cascades for the suppression of S-phase progression. We argue for the need for integrated responses and highlight the potential for oncogenic PTK pathways to bypass the replication checkpoint and contribute to genomic instability.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Victoria, Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Shields
authors.forename: Tony
authors.initials: T
authors.lastname: Tiganis
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D019938:Cyclin D1 / Q000378:metabolism*; D004261:DNA Replication; D006801:Humans; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016196:S Phase; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; D019938:Cyclin D1; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases