WASPs with memory

A tumorigenic culprit in ES cells n the debate over whether ES cells or somatic stem cells have better prospects for stem cell therapies, ES cell proponents admit that their pluripotent cells carry an increased risk: ES cells can form teratomas. have found that a newly discovered Ras gene may be at the heart of this problem. ERas, previously thought to be a pseudogene, was found by the group as being expressed specifically in ES cells. The other genes in this expression class are also expressed in early embryonic tissues such as the inner cell mass and epiblast, but no expression of ERas is evident in the embryo. The lack of phenotype of ERas knockout mice adds to the mystery. Yamanaka suggests that ERas may be I WASPs with memory emory may not be confined to brain cells. have found that the actin polymerization activator WASP has at least the potential to be a memory device. Such a capacity could switch cells into an altered state in which they respond more acutely to a stimulus the second time around. Rosen was intrigued initially by the location of a tyrosine in WASP that others had found was phosphorylated. In structural models, Tyr 291 is buried in the fold that forms in the autoinhibisted form of WASP. Sure enough, Tyr 291 could M In inactive WASP, Tyr 291 (purple) is hidden between two domains. only be phosphorylated (thus further activating WASP activity) when the structure was opened up via addition of the activating Cdc42. Both Tyr 291 phosphor-ylation and Cdc42 activation can be driven by Src family kinases. But Cdc42 activation and opening of WASP take some time, so only a persistent Src signal will still connected to the LIF/Stat3 pathway, which is dispensable for normal mouse development but necessary in ES cells and for the extended survival of mouse blastocysts (a process called diapause). Only in the ES cells and during diapause must pluri-potency be extended past a few days, and this extension may be helped by LIF or ERas expression. The situation is clouded further in humans and monkeys, however, as both have apparently functional ERas genes but lack diapause. Whatever the function of ERas, " ERas null cells should be much safer for clinical applications, " says Yamanaka. ERas has residues characteristic of activated Ras proteins, and is found largely in the activated, GTP-bound form. Its addition transforms cells, …