Research Highlights

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

June 2008

• Cell signalling: A Rac1–JNK2–β-catenin domino cascade

  

  Researchers have found that the small GTPase Rac1 is a crucial component of the canonical Wnt signalling pathway. Reporting in Cell, Fanxin Long and colleagues now show that, in response to Wnt, Rac1 activates Jun N-terminal kinase-2 (JNK2), which phosphorylates β-catenin and promotes its nuclear translocation.

  Original research paper Nature Reviews Molecular Cell Biology 9 424 - 425 doi:10.1038/nrm2412

• Cell signalling: Dynamic redistribution

  

  Although intensively studied, much about Wnt signalling remains enigmatic. Witze et al. report a cell-autonomous mechanism that allows the non-canonical WNT5a pathway to control cell orientation, polarity and directional movement by the redistribution of adhesion receptors.

  Original research paper Nature Reviews Molecular Cell Biology 9 423 doi:10.1038/nrm2413

• Oncogenesis: A sideways move?

  

  Like many other cells, cancer cells can shed membrane-bound microvesicles, although the function of this is not always clear. Janusz Rak, Khalid Al-Nedawi, Brian Meehan and colleagues have evidence in glioblastoma cells that such vesicles can contain an oncogene, which, when taken up by surrounding cells, can contribute to their transformation.

  Original research paper Nature Reviews Cancer 8 408 - 409 doi:10.1038/nrc2405

• Cell migration: The importance of being selective

  

  Phosphoinositide 3-kinases (PI3Ks) are involved in cell signalling and the regulation of cell growth. Class IA PI3K isoforms couple to Tyr kinases and consist of a p110 catalytic subunit (p110α, p110β or p110&948;) that is constitutively bound to one of five distinct p85 regulatory subunits. PI3Ks have been implicated in angiogenesis, but little is known about potential selectivity among the PI3K isoforms or their mechanism of action in endothelial cells during angiogenesis. Bart Vanhaesebroeck and colleagues provide the first in vivo evidence for p110α-isoform selectivity in PI3K signalling during angiogenesis.

  Original research paper Nature Reviews Molecular Cell Biology 9 426 - 427 doi:10.1038/nrm2422

• Innate immunity: Linking hypoxia and NF-κB

  

  The hypoxic response is crucial for tissue homeostasis and cell survival in low oxygen environments, and is essential for the normal function of innate immune cells in oxygen-deprived tissues. It has been established that innate immunity and the hypoxic response are linked at the molecular level, but the exact nature of this link was not previously known. Now, Karin and colleagues have clarified the connection between nuclear factor-κB (NF-κB), a mediator of innate immune responses, and hypoxia-inducible transcription factor 1 (HIF1), an important regulator of hypoxic adaptation, to directly link these two evolutionarily ancient stress responses.

  Original research paper Nature Reviews Immunology 8 401 doi:10.1038/nri2341