Research Highlights

Short, accessible synopses of recent important articles concerning signalling pathways.

February 2007

• Therapy: Escaping inhibition

  

  The success of the ABL-kinase inhibitor imatinib in the treatment of BCR–ABL-driven leukaemia raised hopes that drugs that target key kinases underlying other cancers, such as members of the human epidermal growth factor receptor (HER) family, might be similarly efficacious. However, several small-molecule inhibitors of HER family kinases have shown limited efficacy in HER2-driven breast cancers, despite effective inhibition of kinase activity. Writing in Nature, Natalia Sergina and colleagues now provide an explanation for this phenomenon: failure to completely inhibit the kinase activity of HER2 allows oncogenic signalling through the kinase-inactive family member HER3 to continue.

  Original research paper Nature Reviews Cancer 7 74-75 doi:10.1038/nrc2085

• Cell migration: Chemical detectors or polarity cues?

  

  How do cells translate the spatial information provided by chemoattractant gradients into directed cell movement? Two studies, published in Nature Cell Biology, now show the dynamic accumulation of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P₃) at the leading edge of primary neutrophils during chemotaxis, firmly establishing an important role for PtdIns(3,4,5)P₃ in chemokinesis.

  Original research paper Nature Reviews Molecular Cell Biology 8 93 doi:10.1038/nrm2111

• Nuclear transport: A universal or cargo-selective transport company?

  

  The signal transducers and activators of transcription (STAT) transcription factors are phosphorylated following cytokine stimulation, and they then form homo- or heterodimers, which translocate to the nucleus to control gene expression. The mechanisms of STAT activation and how activated STATs regulate expression of target genes have been extensively characterized. However, the mechanisms of STAT transport to the nucleus are less clear; findings by Kawashima and colleagues now provide new insights.

  Original research paper Nature Reviews Molecular Cell Biology 8 97 doi:10.1038/nrm2109

• Stem cells: Avoiding commitment

  

  Embryonic stem (ES) cells are characterized by pluripotency, the ability to differentiate into any of the three germ-cell layers. In Cell, Szutorisz et al. show that the proteasome, a 'chambered protease' best known for its function in the unfolding and degradation of proteins tagged with ubiquitin, is unexpectedly also important for preventing the inappropriate transcription of genes that promote ES-cell differentiation.

  Original research paper Nature Reviews Molecular Cell Biology 8 99 doi:10.1038/nrm2115

• T cells: Staying in character

  

  Interest by immunologists in the transcription factor FOXP3 (forkhead box P3) rose sharply when it was shown to be crucial for the development of CD4⁺CD25⁺ regulatory T (T_Reg) cells. Now five papers, four published in Nature and one in Nature Immunology, identify some of its key target genes and confirm its important role in maintaining T_Reg-cell characteristics.

  Original research paper Nature Reviews Immunology 7 86 - 87 doi:10.1038/nri2031

• FRETting for a more detailed interactome

  

  A quantitative high-throughput FRET-based method of screening fluorescent protein fusion libraries brings the promise of more detailed interactome maps.

  Original research paper Nature Methods 4 112 - 113 doi:10.1038/nmeth0207-112b