RasGRP4, a New Mast Cell-restricted Ras Guanine Nucleotide- releasing Protein with Calcium- and Diacylglycerol-binding Motifs IDENTIFICATION OF DEFECTIVE VARIANTS OF THIS SIGNALING PROTEIN IN ASTHMA, MASTOCYTOSIS, AND MAST CELL LEUKEMIA PATIENTS AND DEMON

A cDNA was isolated from interleukin 3-developed, mouse bone marrow-derived mast cells (MCs) that con-tained an insert (designated mRasGRP4) that had not been identified in any species at the gene, mRNA, or protein level. By using a homology-based cloning ap-proach, the 2.6-kb hRasGRP4 transcript was also iso-lated from the mononuclear progenitors residing in the peripheral blood of normal individuals. This transcript information was then used to locate the RasGRP4 gene in the mouse and human genomes, to deduce its exon/ intron organization, and then to identify 10 single nu-cleotide polymorphisms in the human gene that result in 5 amino acid differences. The>15-kb hRasGRP4 gene consists of 18 exons and resides on a region of chromo-some 19q13.1 that had not been sequenced by the Hu