Research Highlights

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

October 2008

• Genetics: More than one way....

  

  Now that the human genome has been sequenced, researchers — aided by the rapid development of high-throughput sequencing platforms, as well as other large data analysis systems — can begin to track and understand all genetic changes occurring within a specific type of tumour.

  Original research paper Nature Reviews Cancer 8 742 doi:10.1038/nrc2510

• Membrane trafficking: Endurance of the weakest signal

  

  MET, the Tyr kinase receptor of hepatocyte growth factor (HGF), activates diverse signalling pathways, including AKT/protein kinase B (PKB), extracellular signal-regulated kinase (ERK), Rac and signal transducer and activator of transcription-3 (STAT3). But how are these different downstream pathways specifically regulated and coordinated? Reporting in Journal of Cell Biology, Stephanie Kermorgant and Peter Parker describe an unexpected link between the strength of the signalling response and the trafficking of the receptor and downstream signalling components.

  Original research paper Nature Reviews Molecular Cell Biology 9 742 - 743 doi:10.1038/nrm2519

• Cell division: Back and forth

  

  In contrast to terminally differentiated or senescent cells, quiescent cells retain the ability to resume proliferation following prolonged cell-cycle arrest. Roberts and colleagues now shed light on the mechanism that underlies this reversibility.

  Original research paper Nature Reviews Molecular Cell Biology 9 740 - 741 doi:10.1038/nrm2506

• Cell adhesion: Talin shifts cell spreading into high gear

  

  When suspended fibroblasts encounter a substratum such as fibronectin, they spread and then generate stable sites of cell-substratum contact, or focal adhesions (FAs). The FA protein talin links actin microfilaments to integrins, increasing adhesion by stimulating integrin-fibronectin binding. Talin-1-deficient cells spread and adhere normally due to the compensatory upregulation of talin-2, complicating efforts to understand its role in cell adhesion. In Nature Cell Biology, Zhang et al. now report that talin is a molecular clutch that links the actin cytoskeleton to fibronectin-bound integrins and facilitates the formation of mature FAs.

  Original research paper Nature Reviews Molecular Cell Biology 9 738 doi:10.1038/nrm2517

• Post-translational modification: Picking apart polyubiquitin chains

  

  Polyubiquitin chains are attached to proteins to mediate various cellular processes — Lys63-linked chains often have signalling functions, whereas Lys48-linked chains are associated with protein degradation. Practical limitations, however, have hampered our ability to tease apart the subtler differences between Lys63- and Lys48-linked chains. Polyubiquitin-linkage-specific antibodies, developed by Newton and colleagues, now make it possible to easily discriminate between the different chains. Studies with these antibodies suggest that polyubiquitin editing might be a general mechanism for attenuating signalling.

  Original research paper Nature Reviews Molecular Cell Biology 9 740 - 741 doi:10.1038/nrm2508