Gene interactions and pathways from curated databases and text-mining
Cancer Cell 2008, PMID: 18691551

DNA replication stalling attenuates tyrosine kinase signaling to suppress S phase progression.

Shields, Ben J; Hauser, Christine; Bukczynska, Patricia E; Court, Naomi W; Tiganis, Tony

Here we report that T cell protein tyrosine phosphatase (TCPTP)-dependent and -independent pathways attenuate the JAK and Src protein tyrosine kinases (PTKs) and STAT3 phosphorylation to suppress cyclin D1 expression and S phase progression in response to DNA replication stress. Cells that lack TCPTP fail to suppress JAK1, Src, and STAT3, allowing for sustained cyclin D1 levels and progression through S phase despite continued replication stress. Cells that bypass the checkpoint undergo aberrant mitoses with lagging chromosomes that stain for the DNA damage marker gamma H2AX. Therefore, inactivating JAK, Src, and STAT3 signaling pathways in response to DNA replication stress may be essential for the suppression of S phase progression and the maintenance of genomic stability.

Document information provided by NCBI PubMed

Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • NCI Pathway Database Signaling events mediated by TCPTP: ATR (ATR) → Src (SRC) (positive regulation of S phase of mitotic cell cycle, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Signaling events mediated by TCPTP: ATR (ATR) → STAT3 (dimer)-active complex (STAT3) (positive regulation of S phase of mitotic cell cycle, activates)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Signaling events mediated by TCPTP: Src (SRC) → STAT3 (dimer)-active complex (STAT3) (positive regulation of S phase of mitotic cell cycle, inhibits)
    Evidence: mutant phenotype, assay
  • NCI Pathway Database Signaling events mediated by TCPTP: JAK1 (JAK1) → STAT3 (STAT3) (modification, activates)
    Evidence: mutant phenotype, assay
In total, 4 gene pairs are associated to this article in curated databases