T-cell signalling

ERK5 is a novel type of mitogen-activated protein kinase containing a transcriptional activation domain. Kasler, H. G., Victoria, J., Duramad, O. & Winoto, A. Mol. Cell. Biol. 20 , 8382?8389 (2000) [PubMed]

Mitogen-activated protein kinases (MAPKs) can translocate to the nucleus and activate transcription, but their effects have been assumed to be indirect. Kasler and colleagues now characterize a new type of MAPK ? ERK5 ? that has a potent transcriptional activation domain at its carboxyl terminus, as well as another domain that binds the transcription factor MEF2D. In T cells, maximal activation of MEF2D in response to calcium requires both domains and is blocked by the corepressor Cabin 1.

Cell division

Protein kinase C signalling mediates a program of cell cycle withdrawal in the intestinal epithelium. Frey, M. R. et al. J. Cell Biol. 151 , 763?777 (2000) [Contents page]

Why do most cells stop dividing when they differentiate? In developing intestinal epithelial cells, protein kinase C is activated as the cells climb the intestinal crypts. Frey at al. now couple activation of protein kinase C to a coordinated programme of downstream events: downregulation of mitotic cyclins and altered expression and phosphorylation of retinoblastoma protein and its relatives sends these cells down the pathway to quiescence.

Cellular microbiology

A PEST-like sequence in listeriolysin O essential for Listeria monocytogenes pathogenicity. Decatur, A. L. & Portnoy, D. A. Science 290 , 992?995 (2000) [PubMed]

After Listeria monocytogenes is engulfed by its host cell, it lyses its phagocytic vacuole with the help of a secreted pore-forming toxin called listeriolysin O. This allows the bacterium to escape into the cytosol, where it can rapidly multiply. But what stops the toxin from destroying its home by lysing the plasma membrane too? The answer is simple: listeriolysin O contains a PEST-like sequence that targets it for degradation by the proteasome as soon as it comes in contact with the cytosol.

Protein methylation

Carboxyl methylation of the phosphoprotein phosphatase 2A catalytic subunit promotes its functional association with regulatiory subunits in vivo. Wu, J. et al. EMBO J. 19 , 5672?5681 (2000) [Contents page]

Several proteins can be modified by methylation of their carboxyl termini, but does this alter their function? Wu and colleagues show that it does ? at least for protein phosphatase 2A (PP2A). They identify the yeast enzymes responsible for adding and removing the methyl group and, by manipulating these enzymes genetically, show that methylation alters the affinity of PP2A for different regulatory subunits.