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Abl family kinases are central regulators of multiple cellular processes controlling actin dynamics, proliferation and differentiation. Recent studies indicate that different pathogens highjack Abl kinase signalling to reorganize the host actin cytoskeleton and promote the tyrosine phosphorylation of four known bacterial and viral effector proteins. Abl signalling is implicated in such diverse processes as microbial invasion, viral release from host cells, actin-based motility, actin-rich pedestal formation and cell scattering. Thus, Abl kinases are emerging as crucial regulators of multiple pathological signalling cascades during infection. Therapeutic intervention against Abl kinase activity might be an effective and novel strategy to combat serious microbial diseases.

Directed cortical actin assembly is the driving force for intercellular adhesion. Regulated by phosphorylation, vasodilator-stimulated phosphoprotein (VASP) participates in actin fiber formation. We screened for endothelial proteins, which bind to VASP, dependent on its phosphorylation status. Differential proteomics identified [alpha]II-spectrin as such a VASP-interacting protein. [alpha]II-Spectrin binds to the VASP triple G[P.sub.5]-motif via its SH3 domain, cAMP-dependent protein kinase-mediated VASP phosphorylation at Ser157 inhibits [alpha]II-spectrin-VASP binding. VASP is dephosphorylated upon formation of cell-cell contacts and in confluent, but not in sparse cells, [alpha]II-spectrin colocalizes with nonphosphorylated VASP at cell-cell junctions. Ectopic expression of the [alpha]II-spectrin SH3 domain at cell-cell contacts translocates VASP, initiates cortical actin cytoskeleton formation, stabilizes cell-cell contacts, and decreases endothelial permeability. Conversely, the permeability of VASP-deficient endothelial cells (ECs) and microvessels of VASP-null mice increases. Reconstitution of VASP-deficient ECs rescues barrier function, whereas [alpha]II-spectrin binding-deficient VASP mutants fail to restore elevated permeability. We propose that [alpha]II-spectrin--VASP complexes regulate cortical actin cytoskeleton assembly with implications for vascular permeability.

Structural analyses reveal that the tyrosine kinase interacting protein interacts with the SH3 domains of Src family of tyrosine kinases. Results show that tyrosine kinase interacting protein fragments possessing SH3 proline-rich binding motiff interact with the SH3 domains of the T-cell-specific tyrosine kinase Lck.

The involvement of the c-abl gene in cells' stress response to DNA-damaging agents is demonstrated by its kinase activation when exposed to ionizing radiation. The failure of the c-Abl tyrosine kinase deficient cells to activate the Jun kinase also indicates c-Abl's importance in the stress response. However, c-Abl does not appear to be involved in the response to tumor-necrosis factor because it is not stimulated.

The Src homology domains SH2 and SH3 are modular components present in many signal transduction proteins. They allow rapid formation of stable protein complexes and may also regulate protein function through intramolecular binding events. SH2 domains recognize phosphotyrosyl residues in a specific sequence context, while SH3 domains recognize a PxxP motif and additional residues that mediate binding specificity.

A study was conducted on a cytosolic protein tyrosine kinase (p94) found in HeLA cells. The p94 kinase was observed to have phosphorylated various nonspecific substrates. The kinase was also determined to be quite sensitive to isoflavone genistein inhibition. Two different antisera were used to prove that the HeLa p94 kinase is actually the FER gene product. The results were the first biochemical characterization of the cellular FER gene product.

Abstract SH2 domains are long known prominent players in the field of phosphotyrosine recognition within signaling protein networks. However, over the years they have been joined by an increasing number of other protein domain families that can, at least with some of their members, also recognise pTyr residues in a sequence-specific context. This superfamily of pTyr recognition modules, which includes substantial fractions of the PTB domains, as well as much smaller, or even single member fractions like the HYB domain, the PKCδ and PKCθ C2 domains and RKIP, represents a fascinating, medically relevant and hence intensely studied part of the cellular signaling architecture of metazoans. Protein tyrosine phosphorylation clearly serves a plethora of functions and pTyr recognition domains are used in a similarly wide range of interaction modes, which encompass, for example, partner protein switching, tandem recognition functionalities and the interaction with catalytically active protein domains. If looked upon closely enough, virtually no pTyr recognition and regulation event is an exact mirror image of another one in the same cell. Thus, the more we learn about the biology and ultrastructural details of pTyr recognition domains, the more does it become apparent that nature cleverly combines and varies a few basic principles to generate a sheer endless number of sophisticated and highly effective recognition/regulation events that are, under normal conditions, elegantly orchestrated in time and space. This knowledge is also valuable when exploring pTyr reader domains as diagnostic tools, drug targets or therapeutic reagents to combat human diseases.

Abstract DNAs and proteins are major classes of biomolecules that differ in many aspects. However, a considerable number of their members also share a common architectural feature that enables the assembly of multi-protein complexes and thereby permits the effective processing of signals: loop structures of substantial sizes. Here we briefly review a few representative examples and suggest a functional classification of different types of loop structures. In proteins, these loops occur in protein regions classified as intrinsically disordered. Studying such loops, their binders and their interactions with other loops should reveal much about cellular information computation and signaling network architectures. It is also expected to provide critical information for synthetic biologists and bioengineers.

Abstract Can trustworthy science flourish in countries suffering from dictatorship? This is an increasingly relevant question. Many commercial publishers want to maximise their profits (as is to be expected in a capitalistic system) and are pushing into non-democratic countries with rapid economic growth like China. But how much can we trust the papers coming from countries with dictatorial regimes?

Abstract A considerable number of soluble proteins in cells that biochemists try to analyze are difficult to handle because they seem to behave like sponges that ‘suck up’ many other proteins. We argue here that this behavior is commonly an artifact introduced by the experimenting scientist and that we need to study proteins like animals in the wild: they will only reveal many of their secrets when carefully observed in their largely undisturbed, natural environment. Computational studies that attempt to realistically model cellular protein networks must also factor in the diverse protein habitats to be found in cells.

Abstract This is an in-depth review of the history of quinacrine as well as its pharmacokinetic properties and established record of safety as an FDA-approved drug. The potential uses of quinacrine as an anti-cancer agent are discussed with particular attention to its actions on nuclear proteins, the arachidonic acid pathway, and multi-drug resistance, as well as its actions on signaling proteins in the cytoplasm. In particular, quinacrine's role on the NF-κB, p53, and AKT pathways are summarized.

Abstract This editorial briefly discusses the implications of the recent report by Craig Venter et al. on re-creating Mycoplasma mycoides as a synthetic life form.