Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential.

PDZ-RhoGEF, LARG, and p115RhoGEF are members of a newly identified family of Rho-guanine nucleotide exchange factors (GEFs) exhibiting a unique structural feature consisting of the presence of an area of similarity to regulators of G protein signaling (RGS). This RGS-like (RGL) domain provides a functional motif by which Galpha(12) and Galpha(13) can bind and regulate the activity of these RhoGEFs, thus providing a direct link from these heterotrimeric G proteins to Rho. PDZ-RhoGEF and LARG can also be phosphorylated by tyrosine kinases, including FAK, and associate with Plexin B, a semaphorin receptor, which controls axon guidance during development, through their PDZ domain, thereby stimulating Rho.

Identification of H-Ras, RhoA, Rac1 and Cdc42 responsive genes.

The superfamily of small GTP-binding proteins has expanded dramatically in recent years. The Ras family has long been associated with signaling pathways contributing to normal and aberrant cell growth, while Rho-related protein function is to integrate extracellular signals with specific targets regulating cell morphology, cell aggregation, tissue polarity, cell motility and cytokinesis. Recent findings suggest that certain Rho proteins, including RhoA, Rac1 and Cdc42, can also play a role in signal transduction to the nucleus and cell growth control.

Assessing unmodified 70-mer oligonucleotide probe performance on glass-slide microarrays.

Background: Long oligonucleotide microarrays are potentially more cost- and management-efficient than cDNA microarrays, but there is little information on the relative performance of these two probe types. The feasibility of using unmodified oligonucleotides to accurately measure changes in gene expression is also unclear.

Results: Unmodified sense and antisense 70-mer oligonucleotides representing 75 known rat genes and 10 Arabidopsis control genes were synthesized, printed and UV cross-linked onto glass slides.

Homodimerization and heterodimerization of S1P/EDG sphingosine-1-phosphate receptors.

Sphingosine-1-phosphate (S1P) binds to and signals through several members of a group of G protein-coupled receptors (GPCRs) known as the S1P/EDG family. Several of these receptors are coexpressed in various cell types and recent reports have shown that biological effects of S1P often require more than one S1P receptor subtype. Recent evidence indicates that many GPCRs exist as dimers.

Potent transforming activity of the small GTP-binding protein Rit in NIH 3T3 cells: evidence for a role of a p38gamma-dependent signaling pathway.

A novel branch of the Ras family, Rit, was recently identified. Rit exhibits a distinct C-terminus and effector domain, and does not activate mitogen-activated protein kinase (MAPK) but can cooperate with Raf to transform fibroblasts. Here, we found that when overexpressed, activated mutants of Rit transform NIH 3T3 cells efficiently, and stimulate p38gamma but not MAPK, p38alpha, p38gamma, p38delta, or ERK5.