The bone morphogenetic proteins (BMPs) are a group of transforming growth factor ,B (TGF-Pi)-related factors whose only receptor identified to date is the product of the daf-4 gene from Caenorhabditis elegans. Mouse embryonic NIH 3T3 fibroblasts display high-affinity 125I-BMP-4 binding sites. Binding assays are not possible with the isoform 125I-BMP-2 unless the positively charged N-terminal sequence is removed to create a modified BMP-2, 125I-DR-BMP-2. Cross-competition experiments reveal that BMP-2 and BMP-4 interact with the same binding sites. Affinity cross-linking assays show that both BMPs interact with cell surface proteins corresponding in size to the type I (57-to 62-kDa) and type II (75-to 82-kDa) receptor components for TGF-, and activin. Using a PCR approach, we have cloned a cDNA from NIH 3T3 cells which encodes a novel member of the transmembrane serine/threonine kinase family most closely resembling the cloned type I receptors for TGF-,B and activin. Transient expression of this receptor in COS-7 cells leads to an increase in specific 125I-BMP4 binding and the appearance of a major affinity-labeled product of -64 kDa that can be labeled by either tracer. This receptor has been named BRK-1 in recognition of its ability to bind BMP-2 and BMP-4 and its receptor kinase structure. Although BRK-1 does not require cotransfection of a type II receptor in order to bind ligand in COS cells, complex formation between BRK-1 and the BMP type II receptor DAF-4 can be demonstrated when the two receptors are coexpressed, affinity labeled, and immunoprecipitated with antibodies to either receptor subunit. We conclude that BRK-1 is a putative BMP type I receptor capable of interacting with a known type II receptor for BMPs.The transforming growth factor ,B (TGF-,B) superfamily contains a large number of growth, differentiation, and morphogenetic cytokines that are active as homo-or heterodimers.This superfamily includes the TGF-1 family, the activin family, the Mullerian inhibiting substance (MIS), and the bone morphogenetic protein (BMP)/Vg family, which composes the largest group (reviewed in reference 39). Human BMP-2 and BMP-4 and their Drosophila homolog dpp are highly related (74 to 76% sequence identity [72]), as are BMP-5, BMP-6, and BMP-7 and their Drosophila homolog 60A (69 to 73% sequence identity [21]). Given the high degree of structural similarity among these family members, it is expected that their receptors will also form a family of related molecules. activin (2, 40) have been cloned. It has recently been determined that the product of the daf-4 gene from Caenorhabditis elegans, which is involved in both inhibition of dauer larva formation and exit from the dauer stage, is a type II receptor for BMP-2 and BMP-4 (24). Each of these receptors is predicted to be a transmembrane serine/threonine kinase. Ligand binding to each of these type II receptors in a variety of cell types does not appear to require coexpression of additional receptor components, indicating that type II receptors are capable of...

Rhinovirus infection significantly alters the expression of many genes associated with the immune response, including chemokines and antivirals. The data obtained provide insights into the host response to rhinovirus infection and identify potential novel targets for further evaluation.

Despite the expected heterogeneity of the disorder, differences in mucosal chemokine signalling were evident in this cross-sectional study of IBS patients at the level of both gene expression and protein secretion, with IBS patients demonstrating a consistent deficit in the expression and secretion of chemokines known to play a critical role in mucosal defence.

Exposure to some compounds with estrogenic activity, during fetal development, has been shown to alter development of reproductive organs, leading to abnormal function and disease either after birth or during adulthood. In order to understand the molecular events associated with the estrogenicity of different chemicals and to determine whether common sets of gene expression changes can be predictive of estrogenic activity, we have used microarray technology to determine the transcriptional program influenced by exposure to this class of compounds during organogenesis and development. Changes in patterns of gene expression were determined in the developing uterus and ovaries of Sprague-Dawley rats on GD 20, exposed to graded dosages (sc) of 17alpha-ethynyl estradiol (EE), genistein, or bisphenol A (BPA) from GD 11 to GD 20. Dose levels were roughly equipotent in estrogenic activity. We compared the transcript profiles between treatment groups and controls, using oligonucleotide arrays to determine the expression level of approximately 7000 rat genes and over 1000 expressed squence tags (ESTs). At the highest tested doses of EE, BPA, or genistein, we determined that less than 2% of the mRNA detected by the array showed a 2-fold or greater change in their expression level (increase or decrease). A dose-dependent analysis of the transcript profile revealed a common set of genes whose expression is significantly and reproducibly modified in the same way by each of the 3 chemicals tested. Additionally, each compound induces changes in the expression of other transcripts that are not in common with the others, which indicated not all compounds with estrogenic activity act alike. The results of this study demonstrate that transplacental exposure to chemicals with estrogenic activity changes the gene expression profile of estrogen-sensitive tissues, and that the analysis of the transcript profile of these tissues could be a valuable approach to determining the estrogenicity of different compounds.

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