Research Highlights

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

August 2008

• Cell signalling: Sensing nutrient availability

  

  The mammalian target of rapamycin (mTOR) protein complexes regulate cell growth in response to nutrients. However, the first step of this pathway (how nutrients regulate activation of mTOR complexes) has remained unknown. Two recent reports now show that Rag GTPases functionally interact with mTOR complex-1 (mTORC1) and are necessary for the activation of the mTORC1 pathway by amino acids.

  Original research paper Nature Reviews Molecular Cell Biology 9 586 doi:10.1038/nrm2452

• Cell signalling: AKTing in Wnt pathway

  

  The Wnt-β-catenin pathway is pivotal for numerous important cellular events during embryonic development, tissue homeostasis and tumorigenesis. β-catenin enters the nucleus following Wnt stimulation, and acts as a transcriptional coactivator by binding to T-cell factor/lymphoid enhancer factor (TCF/LEF). Nuclear import and export of β-catenin represents a crucial step in regulating signalling-competent β-catenin levels, as this protein exerts its signalling activity only in the nucleus. Takemaru and colleagues now unravel a novel mechanism that controls the dynamic nucleo-cytoplasmic trafficking of β-catenin.

  Original research paper Nature Reviews Molecular Cell Biology 9 584 doi:10.1038/nrm2462

• Cell cycle: Achieving entry

  

  Whereas the accumulation of cyclins triggers mitotic entry in embryonic cells, the trigger in somatic cells has been elusive. Reporting in Science, Guowei Fang and colleagues now show that Bora, a protein that participates in asymmetric cell division, and the kinase Aurora A synergistically activate Polo-like kinase-1 (PLK1) and thereby induce mitotic entry in somatic cells.

  Original research paper Nature Reviews Molecular Cell Biology 9 587 doi:10.1038/nrm2454

• Angiogenesis: Survival of the infected

  

  The development of Kaposi sarcoma, a highly vascular tumour of endothelial cell origin, is associated with a herpes virus, KSHV (Kaposi sarcoma-associated herpesvirus). Individual KSHV genes have been shown to upregulate the phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR, also known as FRAP1) pathway. Ling Wang and Blossom Damania have examined the role of this signalling pathway in endothelial cell survival and angiogenesis in response to the whole virus.

  Original research paper Nature Reviews Cancer 8 569 doi:10.1038/nrc2452

• Angiogenesis: TGF makes a new friend

  

  Our understanding of angiogenesis and vasculogenesis has mushroomed in the last two decades, yielding molecular data that have allowed the development of clinically useful therapeutic agents. Despite these successes, a complete appreciation of how individual angiogenic pathways interact and cooperate remains an important goal. Redondo and colleagues have made some headway towards realizing this goal by identifying a novel link between two important effectors of tumour angiogenesis: transforming growth factor β(TGFβ) and prostaglandin E2 (PGE2).

  Original research paper Nature Reviews Cancer 8 572 doi:10.1038/nrc2448