Role of Sema4C in TGF-β1-induced mitogen-activated protein kinase activation and epithelial–mesenchymal transition in renal tubular epithelial cells

Background. The p38 mitogen-activated protein kinase (p38 MAPK) is an important intracellular signal transduction pathway involved in TGF-β1-induced epithelial–mesenchymal transition (EMT). Sema4C, a member of the semaphorin family, was found to be essential for the activation of p38 MAPK. However, the role of Sema4C in promoting TGF-β1-induced EMT is unclear

Two Factor Reprogramming of Human Neural Stem Cells into Pluripotency

BACKGROUND:Reprogramming human somatic cells to pluripotency represents a valuable resource for the development of in vitro based models for human disease and holds tremendous potential for deriving patient-specific pluripotent stem cells. Recently, mouse neural stem cells (NSCs) have been shown capable of reprogramming into a pluripotent state by forced expression of Oct3/4 and Klf4; however it has been unknown whether this same strategy could apply to human NSCs, which would result in more relevant pluripotent stem cells for modeling human disease. METHODOLOGY AND PRINCIPAL FINDINGS:Here, we show that OCT3/4 and KLF4 are indeed sufficient to induce pluripotency from human NSCs within a two week time frame and are molecularly indistinguishable from human ES cells. Furthermore, human NSC-derived pluripotent stem cells can differentiate into all three germ lineages both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE:We propose that human NSCs represent an attractive source of cells for producing human iPS cells since they only require two factors, obviating the need for c-MYC, for induction into pluripotency. Thus, in vitro human disease models could be generated from iPS cells derived from human NSCs

Potential disease targets for drugs that disrupt protein-- protein interactions of Grb2 and Crk family adaptors.

This review summarises some of the knowledge we have about Crk and Grb2 family adaptor protein signalling in health and disease and outlines the current status and the challenges still remaining in the development of efficient and selective inhibitors of their protein - protein interactions. It also highlights briefly some recent successes and problems of inhibitors for proteins that functionally interact with Crk and Grb2 family adaptors, as well as opportunities, which may arise from combination therapies. Grb2 and Crk family adaptors regulate signalling pathways linked to human diseases. They are mainly composed of Src homology 2 (SH2) and Src homology 3 (SH3) domains, which serve as docking sites for signalling proteins, including various receptors, cytoplasmic kinases and GTPase regulators. Considerable insight into the biological functions and mechanisms of action of small SH2/SH3 domain adaptors has been gained in the last years from experimental approaches as diverse as targeted gene disruption and structural studies at the atomic level. This has already indicated several strategies to utilise SH2 and SH3 domain interaction inhibitors in human disease therapy. Additional molecular targets for Crk and Grb2 domain interaction blockers are expected to surface as further protein-protein interactions are discovered. Examples include newly found DOCK family proteins (DOCK3, DOCK4, and DOCK5) which are known or suspected effectors of Crk proteins and the interaction of Grb2 with the cell cycle regulator p27Kip1

What's in a loop?

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

Very 'sticky' proteins - not too sticky after all?

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

Very ‘sticky’ proteins – not too sticky after all?

<p>Abstract</p> <p>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.</p

What's in a loop?

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

What’s in a loop?

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.</p