High impact information on RASGRP2

• These results establish that ES cells are a ready source of mature megakaryocytes for integrin studies and other biological applications, and they implicate CalDAG-GEFI in inside-out signaling to alphaIIbbeta3 [1].
• Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling [1].
• We now report the cloning of a brain-enriched gene, CalDAG-GEFI, which has substrate specificity for Rap1A, dual binding domains for calcium (Ca2+) and diacylglycerol (DAG), and enriched expression in brain basal ganglia pathways and their axon-terminal regions [2].
• In addition, CalDAG-GEFI-deficient platelets showed defective integrin alpha2beta1-dependent adhesion and spreading [3].
• Moreover, integrin alpha2beta1 engagement failed to trigger Rap1b activation in murine platelets lacking CalDAG-GEFI, a guanine nucleotide exchange factor regulated by Ca2+ and diacylglycerol, despite normal phosphorylation and activation of PLCgamma2 [3].

Anatomical context of RASGRP2

• However, prolonged exposure to phorbol esters, or growth in serum, results in localization of CalDAG-GEFI to the cell membrane and restoration of Ras exchange activity [4].
• In contrast, CalDAG-GEFI is localized predominantly to the cytosol and lacks Ras exchange activity in vivo [4].
• Here, we show that CalDAG-GEFI and CalDAG-GEFII mRNAs, detected by in situ hybridization analysis, have sharply contrasting forebrain-predominant distributions in the mature brain: CalDAG-GEFI is expressed mainly in the striatum and olfactory structures and deep cortical layers, whereas CalDAG-GEFII is expressed widely in the forebrain [5].

Associations of RASGRP2 with chemical compounds

• A CalDAG-GEFI/Rap1/B-Raf cassette couples M(1) muscarinic acetylcholine receptors to the activation of ERK1/2 [6].
• Guanine nucleotide exchange factors CalDAG-GEFI and CalDAG-GEFII are colocalized in striatal projection neurons [5].

References