Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75)

The non-receptor tyrosine kinase Src is a critical regulator of cytoskeletal contraction, cell adhesion, and migration. In normal cells, Src activity is stringently controlled by Csk-dependent phosphorylation of Src(Y530), and by Cullin-5-dependent ubiquitinylation, which affects active Src(pY419) exclusively, leading to its degradation by the proteosome. Previous work has shown that Src activity is also limited by Cdk5, a proline-directed kinase, which has been shown to phosphorylate Src(S75). Here we show that this phosphorylation promotes the ubiquitin-dependent degradation of Src, thus restricting the availability of active Src. We demonstrate that Src(S75) phosphorylation occurs in vivo in epithelial cells, and like ubiquitinylation, is associated only with active Src. Preventing Cdk5-dependent phosphorylation of Src(S75), by site-specific mutation of S75 or by Cdk5 inhibition or suppression, increases Src(Y419) phosphorylation and kinase activity, resulting in Src-dependent cytoskeletal changes. In transfected cells, ubiquitinylation of Src(S75A) is about 35% that of wild-type Src-V5, and its half-life is approximately 2.5-fold greater. Cdk5 suppression leads to a comparable decrease in the ubiquitinylation of endogenous Src and a similar increase in Src stability. Together, these findings demonstrate that Cdk5-dependent phosphorylation of Src(S75) is a physiologically significant mechanism of regulating intracellular Src activity.     

Transforming growth factor-β-inducible early response gene 1 is a novel substrate for atypical protein kinase Cs

The protein kinase C (PKC) family of serine/threonine kinases consists of ten different isoforms grouped into three subfamilies, denoted classical, novel and atypical PKCs (aPKCs). The aPKCs, PKCι/λ and PKCζ serve important roles during development and in processes subverted in cancer such as cell and tissue polarity, cell proliferation, differentiation and apoptosis. In an effort to identify novel interaction partners for aPKCs, we performed a yeast two-hybrid screen with the regulatory domain of PKCι/λ as bait and identified the Krüppel-like factors family protein TIEG1 as a putative interaction partner for PKCι/λ. We confirmed the interaction of both aPKCs with TIEG1 in vitro and in cells, and found that both aPKCs phosphorylate the DNA-binding domain of TIEG1 on two critical residues. Interestingly, the aPKC-mediated phosphorylation of TIEG1 affected its DNA-binding activity, subnuclear localization and transactivation potential.     

Ca2+ channel modulation by 8-bromocyclic AMP in cultured heart cells

Modulation of ion channels is of increasing interest as it is an important step in the regulation of cellular functions. We have analysed the effect of 8-bromocyclic AMP on Ca2+ channels in cultured cardiac cells by the patch-clamp method and report here that there was a large increase in the probability of opening of the channels. On the basis of a recently proposed kinetic reaction scheme we suggest that cyclic AMP-dependent phosphorylation of Ca2+ channels primarily promotes the forward rate constants which lead to the open state of a Ca2+ channel during depolarization.     

Nonlinear limits to the information capacity of optical fibre communications.

The exponential growth in the rate at which information can be communicated through an optical fibre is a key element in the 'information revolution'. However, as for all exponential growth laws, physical limits must be considered. The nonlinear nature of the propagation of light in optical fibre has made these limits difficult to elucidate. Here we use a key simplification to investigate the theoretical limits to the information capacity of an optical fibre arising from these nonlinearities. The success of our approach lies in relating the nonlinear channel to a linear channel with multiplicative noise, for which we are able to obtain analytical results. In fundamental distinction to linear channels with additive noise, the capacity of a nonlinear channel does not grow indefinitely with increasing signal power, but has a maximal value. The ideas presented here may have broader implications for other nonlinear information channels, such as those involved in sensory transduction in neurobiology. These have been often examined using additive noise linear channel models but, as we show here, nonlinearities can change the picture qualitatively.     

Atomic structure holography using thermal neutrons.

The idea of atomic-resolution holography has its roots in the X-ray work of Bragg and in Gabor's electron interference microscope. Gabor's lensless microscope was not realized in his time, but over the past twelve years there has been a steady increase in the number of reports on atomic-resolution holography. All of this work involves the use of electrons or hard X-rays to produce the hologram. Neutrons are often unique among scattering probes in their interaction with materials: for example, the relative visibility of hydrogen and its isotopes is a great advantage in the study of polymers and biologically relevant materials. Recent work proposed that atomic-resolution holography could be achieved with thermal neutrons. Here we use monochromatic thermal neutrons, adopting the inside-source concept of Sz?ke, to image planes of oxygen atoms located above and below a single hydrogen atom in the oxide mineral simpsonite.     

Formation of coastline features by large-scale instabilities induced by high-angle waves.

Along shore sediment transport that is driven by waves is generally assumed to smooth a coastline. This assumption is valid for small angles between the wave crest lines and the shore, as has been demonstrated in shoreline models. But when the angle between the waves and the shoreline is sufficiently large, small perturbations to a straight shoreline will grow. Here we use a numerical model to investigate the implications of this instability mechanism for large-scale morphology over long timescales. Our simulations show growth of coastline perturbations that interact with each other to produce large-scale features that resemble various kinds of natural landforms, including the capes and cuspate forelands observed along the Carolina coast of southeastern North America. Wind and wave data from this area support our hypothesis that such an instability mechanism could be responsible for the formation of shoreline features at spatial scales up to hundreds of kilometres and temporal scales up to millennia.     

Mars' volatile and climate history.

There is substantial evidence that the martian volatile inventory and climate have changed markedly throughout the planet's history. Clues come from areas as disparate as the history and properties of the deep interior, the composition of the crust and regolith, the morphology of the surface, composition of the present-day atmosphere, and the nature of the interactions between the upper atmosphere and the solar wind. We piece together the relevant observations into a coherent view of the evolution of the martian climate, focusing in particular on the observations that provide the strongest constraints.