Ask about this productRelated genes to: RASGRP2 antibody
- Gene:
- RASGRP2 NIH gene
- Name:
- RAS guanyl releasing protein 2
- Previous symbol:
- -
- Synonyms:
- CALDAG-GEFI
- Chromosome:
- 11q13.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-21
- Date modifiied:
- 2019-04-23
Related products to: RASGRP2 antibody
Related articles to: RASGRP2 antibody
- Hemostasis and thrombosis are strongly dependent on the unique ability of platelets to rapidly activate integrin receptors and to firmly adhere to sites of injury under shear stress conditions. Central to integrin activation is the small GTPase RAP1, which itself is activated by guanine nucleotide exchange factors (GEFs). CalDAG-GEFI (RASGRP2) is the highest expressed and functionally dominant platelet RAP-GEF. However, a genome-wide association study also suggested a significant role for RAPGEF2 (PDZ-GEFI), a low expressed RAP-GEF, in human platelet aggregation. Here, we used mice deficient in RAPGEF2 (megakaryocyte-specific, Rapgef2mKO), CalDAG-GEFI (Caldaggef1-/-), or both RAPGEF2 and CalDAG-GEFI (DKO) to characterize the contribution of RAPGEF2 signaling to platelet function, hemostasis and thrombosis. RAPGEF2 protein was detected in murine and human platelets. Compared to control or Caldaggef1-/- platelets, both RAP1 activation and integrin aIIbb3-mediated aggregation were significantly diminished in DKO platelets. When compared to controls, Rapgef2mKO platelets exhibited reduced integrin activation, a more reversible aggregation response, and impaired adhesion under conditions of shear stress ex vivo and in vivo. Mechanistic studies strongly suggest that RAPGEF2 operates downstream of receptors coupled to the heterotrimeric G protein, G13 (GNA13), such as aIIbb3 and the thromboxane receptor. Together, our studies provide genetic evidence that RAPGEF2 in platelets operates downstream of G13 as an important regulator of RAP1 signaling and integrin activation, especially under conditions of elevated shear stress. These findings markedly improve our understanding of G protein signaling and integrin function in platelets, with potential implications for the development of improved platelet-targeted therapies for cardiovascular disease. - Source: PubMed
Publication date: 2026/04/08
Paul David SRocco David JClark Emily GSchug Wyatt JMartyanov Alexey AVander Ploeg Matthew RJones Summer RLee Robert HMwiza Jean Marie NBallard-Kordeliski AbigailDeger NazliKawano TomohiroMackman NigelBergmeier Wolfgang - Immediate-early gene (IEG) induction guides elucidation of signaling pathways mediating neuronal plasticity underlying compulsive use of psychostimulants. IEG induction after psychostimulant administration has been attributed to both PKA- and RapGEF2-dependent signaling pathways initiated by D1 receptor stimulation by dopamine. However, it is not clear how each pathway contributes individually to IEG induction, dopaminoceptive neuronal activity, and neuronal plasticity. We used Cre-LoxP technology and a novel Cre-amplifier transgene to delete RapGEF2 only in D1-MSNs, and investigate its role in cocaine-induced IEG and behavioral responses. D1-MSN-specific RapGEF2 deletion blocked cocaine-induced ERK phosphorylation and Egr-1 induction, without affecting cocaine self-administration or c-Fos induction by cocaine. Deletion of Rap1 in D1-MSNs blocked cocaine-induced p-ERK and Egr-1 expression, but not the induction of c-Fos. Like RapGEF2 deletion, Rap1 deletion from D1-MSNs had no effect on final maintenance of stable cocaine self-administration, although the rate of acquisition was significantly impaired. These results suggest that D1-dependent activation of Egr1 is not ultimately required for cocaine self-administration, although it may affect the behavioral dynamics of this process. Suppressing cAMP elevation in D1-MSNs by D1-specific expression of PDE4D3-cat greatly reduced induction of both Egr-1 and c-Fos in NAc after cocaine administration, demonstrating that induction of both IEGs requires cAMP elevation in D1-MSNs. Specific inhibition of PKA activity via PKI-alpha expression in D1-MSNs also blocked both c-Fos and Egr-1 induction. Thus, acute or chronic cocaine administration activates at least two separate cAMP effectors in D1-MSNs. PKA activation leads to c-Fos induction, likely through CREB, and to Egr1 activation via Rap1, likely through a previously reported dependence on RasGRP2. RapGEF2 activation leads exclusively to Egr1 induction. The finding that PKA activates the ERK-Egr-1 signaling pathway by convergence on Rap1, and concomitantly activates c-Fos independently of Rap1, may underlie selective effects of RapGEF2 and PKA inhibition on psychostimulant-dependent behaviors in mice. - Source: PubMed
Zhang Hai-YingSalman TabindaBi Guo-HuaJiang Sunny ZGerfen Charles RLutas AndrewXu WenqinXi Zheng-XiongEiden Lee E - Ovarian cancer is a rare cancer, it has the worst prognosis and the highest mortality rate, especially in high-grade serous ovarian cancer (HGSOC). High-throughput data generation is developed and provides an opportunity to investigate molecular pathways involved in cancer progression. The purpose of this study is to explore the role of main genes linked to the immune system and immune microenvironment in HGSOC using bioinformatics approaches to introduce promising biomarkers. - Source: PubMed
Publication date: 2025/11/28
Fatehi RaziehTabatabaiefar MohammadAminBehnamfar FaribaKhanahmad Hossein - Inherited platelet function disorders (IPFD) are characterized by normal platelet count and morphology but impaired function due to pathogenic variants in genes encoding membrane receptors, granule constituents, or intracellular signaling proteins. Glanzmann's thrombasthenia, the most representative IPFD, results from or mutations that disrupt the αIIbβ3 integrin complex, producing severe mucocutaneous bleeding. Advances in molecular genetics have expanded the IPFDs landscape to include defects in other platelet receptors (Glycoprotein (GP)-VI, P2Y, and thromboxane A[TxA]-R), signaling mediators (RASGRP2, FERMT3, G-protein regulators, PLC, and TxA pathway enzymes), and granule biogenesis disorders such as Hermansky-Pudlak and Chediak-Higashi syndromes. High-throughput sequencing technologies, including long-read approaches, have greatly improved diagnostic yield and clarified genotype-phenotype correlations. Clinically, bleeding severity varies from mild to life-threatening, and management relies on antifibrinolytics, desmopressin, or platelet transfusion; recombinant activated factor VII and hematopoietic stem cell transplantation are reserved for selected cases. Emerging strategies such as gene therapy and bispecific antibodies that link platelets and coagulation factors represent promising advances toward targeted and preventive treatment. A better knowledge of the clinical features and understanding molecular pathogenesis of IPFDs not only enhances diagnostic precision and therapeutic options but also provides key insights into platelet biology, intracellular signaling, and the broader mechanisms of human hemostasis. - Source: PubMed
Publication date: 2025/10/30
Rodríguez-Alén AgustínMoscardó AntonioBastida José MRivera José - - Source: PubMed
Publication date: 2025/09/30
Mousa JehanNayfeh TarekBilalaga Mariah MalakProkop LarryHarahsheh Ehab YOlarewaju Bukola AAbbas Mohammed TiseerCrowe Monica MAlexander Erin ROsundiji Oluwabusayo MAsif Misha BDhamija RadhikaCamoriano John KMoyer Ann MOsundiji Mayowa A