Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors.

Bone morphogenetic proteins (BMPs) comprise the largest subfamily of TGF-beta-related ligands and are known to bind to type I and type II receptor serine/threonine kinases. Although several mammalian BMP type I receptors have been identified, the mammalian BMP type II receptors have remained elusive. We have isolated a cDNA encoding a novel transmembrane serine/threonine kinase from human skin fibroblasts which we demonstrate here to be a type II receptor that binds BMP-4.

Characterization and cloning of a receptor for BMP-2 and BMP-4 from NIH 3T3 cells.

The bone morphogenetic proteins (BMPs) are a group of transforming growth factor beta (TGF-beta)-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.

The mechanism for the rapid desensitization in bradykinin-stimulated inositol monophosphate production in NG108-15 cells involves interaction of a single receptor with multiple signaling pathways.

We have previously shown that the mechanism for the rapid desensitization in bradykinin (BDK)-stimulated inositol monophosphate (IP) production in NG108-15 cells involves both a rapid loss of receptors from the cell surface and an uncoupling of the receptor:G-protein:phospholipase C (PLC) signaling process, with protein kinase C (PKC) activation playing a role only at a postreceptor level (Wolsing and Rosenbaum, 1991). In contrast to BDK, a 5-min pretreatment with the BDK receptor "antagonist" NPC-567 is sufficient to cause a substantial decrease in the subsequent BDK maximal response (Emax) without altering either the BDK potency (EC50) or the BDK receptor number. An 18-hr pretreatment of the cells with 200 ng/ml pertussis toxin (PT) does not alter the BDK response (Fold stim = 2.

Characterization of the RDC1 gene which encodes the canine homolog of a proposed human VIP receptor. Expression does not correlate with an increase in VIP binding sites.

We have isolated a portion of the canine gene encoding the orphan receptor RDC1 [1]. The complete coding sequence is contained in a single exon, and an intron divides the 5' untranslated region of RDC1 mRNA. The RDC1 protein is 94% homologous to the gene product of GPRN1, which has been proposed to serve as a VIP receptor when expressed in CHO-K1 and COS-7 cells (Sreedharan, S.

Bradykinin-stimulated inositol phosphate production in NG108-15 cells is mediated by a small population of binding sites which rapidly desensitize.

[3H]Bradykinin (BDK) binds to two distinct binding sites (P less than .01, N = 12) in NG108-15 cell membranes; (site 1: Kd1 = 3.09 x 10(-10) M, Bmax1 = 242 +/- 24 fmol/mg protein) and (site 2: Kd2 = 1.