Cloning of rat Ras guanine nucleotide releasing protein 4, and evaluation of its expression in rat mast cells and their bone marrow progenitors.
We recently cloned a new mast cell (MC) restricted, Ras guanine nucleotide releasing protein (designated mRasGRP4) from IL-3-developed, mouse bone marrow-derived MCs that can activate varied members of the Ras superfamily of small GTP-binding proteins. We now describe the rat ortholog of this MC-specific guanine exchange factor. Using the mRasGRP4 gene and transcript in a homology-based cloning approach, the relevant transcript was isolated and sequenced from the spleen and lungs of Sprague-Dawley rats. Evidence for differential splicing of the rRasGRP4 transcript was obtained in the spleen. The rat basophilic leukemia 1 MC line was found to express rRasGRP4, as well as the MC-committed progenitors residing in the bone marrow and the mature MCs residing in varied tissues of Sprague-Dawley rats. Based on its deduced amino acid sequence, rRasGRP4 is 93% identical to mRasGRP4. rRasGRP4 contains all of the functional domains present in the RasGRP family of guanine nucleotide exchange factors. Like its mouse ortholog, rRasGRP4 is a MC-restricted guanine exchange factor that contains Ca(2+) and phorbol ester/diacylglycerol-binding domains C-terminal of its CDC25-like catalytic domain.
Li
Lixin
L
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Yang
Yi
Y
Stevens
Richard L
RL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D020666:ras-GRF1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
C475665:Ras guanine nucleotide releasing protein 4, rat; D020666:ras-GRF1