Ask about this productRelated genes to: SHOC2 antibody
- Gene:
- SHOC2 NIH gene
- Name:
- SHOC2 leucine rich repeat scaffold protein
- Previous symbol:
- -
- Synonyms:
- KIAA0862, SOC2, SUR-8, SOC-2, SUR8
- Chromosome:
- 10q25.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-03-30
- Date modifiied:
- 2019-04-23
Related products to: SHOC2 antibody
Related articles to: SHOC2 antibody
- Noonan syndrome (NS) is the most common RASopathy, a developmental disorder that derives from dysregulation of the mitogen-activated protein kinase (MAPK) pathway. NS results from modestly activating mutations in proteins throughout the pathway. Trametinib, a MEK inhibitor, has shown promising results for certain NS complications, but NS-specific therapeutic options are lacking. CRAF activity, which is governed by the adaptor protein 14-3-3, represents a key NS regulatory node that has not been exploited. When phosphorylated (p) at CRAF S259, the 14-3-3/CRAF-pS259 complex adopts an inactive conformation in which CRAF does not fully bind to RAS or to other RAFs. NS mutations in CRAF occur at residues surrounding S259 (CRAF). Here, we quantify how these mutations impair 14-3-3/CRAF, both through decreased phosphorylation (64 to 97%) and decreased binding affinity to 14-3-3 (three- to >100-fold decrease). We also explore the potential of restoring homeostasis in NS using molecular glues (MGs) to enhance the 14-3-3/CRAF inhibitory complex. We report that MGs protect phosphorylation of CRAF-pS259 in CRAF-effector NS mutant backgrounds. They also stabilize 14-3-3/CRAF interactions and increase the levels of S259 phosphorylation up to 2.8-fold, leading to decreased association of CRAF with NRAS and decreased formation of the active CRAF kinase dimers. Ultimately, inhibition of CRAF activation leads to decreased phosphorylation of the downstream target ERK, similarly to trametinib, in three different NS variants (activation of the phosphatase SHOC2, CRAF, and CRAF). These results reveal a potential therapeutic strategy for NS and related RASopathies. They also demonstrate the scope and limitations of stabilizing mutation-weakened complexes with molecular glues. - Source: PubMed
Publication date: 2026/04/28
Virta Johanna MVickery Holly RKonstantinidou MarkellaCrawford Mckenna CPennings Marloes A MOttmann ChristianBrunsveld LucArkin Michelle R - Kinase-mediated phosphorylation is crucial for thermal adaptation. While extracellular signal-regulated kinase 1/2 (ERK1/2) signaling is well characterized in model organisms, its functional divergence and genetic regulation in marine species with distinct thermal adaptations remain poorly understood. In this study, we investigated the genetic basis of differential ERK activation under heat stress using two oyster subspecies from distinct thermal niches: Crassostrea gigas and Crassostrea angulata. Combining ERK inhibition assays with heat stress treatments, followed by proteomic and phosphoproteomic profiling, we constructed a heat-responsive ERK network and identified that ERK phosphorylates ATP-dependent 6-phosphofructokinase (PFK) at Thr775, enhancing its enzymatic activity and glycolytic capacity. Genome-wide association analysis further revealed that a synonymous mutation in the leucine-rich repeat protein SHOC2 drives divergent ERK phosphorylation patterns between the two subspecies by altering RNA structure and expression. Our findings demonstrated that the heat-responsive SHOC2-BRAF-ERK-PFK cascade exhibits stronger activation in thermotolerant species, enabling marine ectotherms to fine-tune metabolic responses to temperature variation. This study serves as an experimental case elucidating how genetic variations shape thermal adaptation divergence through phosphorylation-mediated regulation, thereby providing a molecular framework for adaptive mechanisms of climate variability. - Source: PubMed
Publication date: 2026/04/20
Wang MinWang ChaogangDu MingyangJiang ZhuxiangChen JinchengPang MeiqianZhang TaipingCong RihaoWang WeiZhang GuofanLi Li - This study aimed to describe the clinical manifestations and genetic variants of Noonan syndrome in a Colombian pediatric population and to identify the genes most frequently associated with specific phenotypic features. - Source: PubMed
Publication date: 2026/04/16
Martínez Rueda Silvia CDel Pilar Montilla MariaBaquero CarolinaGómez SusanaLopera Maria VictoriaZuluaga Nora AlejandraForero Adriana CarolinaGiraldo GustavoPineda Trujillo NicolásMartínez Juan CamiloDurán Ventura PaolaAlfaro Juan Manuel - An interplay of growth factors and signaling pathways governs the development and maintenance of lymphatic vasculature, ensuring proper fluid homeostasis and immune function. Disruption of these regulatory mechanisms can lead to congenital lymphatic disorders and contribute to various pathological conditions. However, the mechanisms underlying the molecular regulation of these processes remain elusive. Here, we reveal a critical and previously unappreciated role for the signaling scaffold protein Shoc2 in lymphangiogenesis. We demonstrate that loss of Shoc2 results in near-complete loss of lymphatic vasculature in vivo and senescence of lymphatic endothelial cells in vitro. Mechanistically, Shoc2 is required for balancing signaling through the ERK1/2 pathway, and its loss results in increased mTORC1 signaling. This dysregulation impairs mitochondrial respiration and triggers an IRF/IFN-II response, ultimately leading to cellular senescence. Strikingly, expression of the Noonan Syndrome with Loose anagen Hair (NSLH)-causing Shoc2 variant S2G phenocopies the effects of Shoc2 loss. Together, these studies establish the critical role of Shoc2 in lymphangiogenesis and uncover a novel mechanistic link between Shoc2 signaling, mitochondrial function, innate immune response, and lymphatic development, with significant implications for Ras-pathway-related congenital disorders. - Source: PubMed
Publication date: 2026/04/07
Wilson PatriciaVishwakarma VishakhaNorcross RebeccaKhaire KashmiraPham Van NWeinstein Brant MJung Hyun MinGalperin Emilia - Genomic ascertainment of electronic health record-linked exome data was used to quantify germline pathogenic/likely pathogenic variant prevalence, cancer prevalence, and survival in adults with non-NF1 RAS/mitogen-activated protein kinase genes (RASopathies). - Source: PubMed
Publication date: 2026/03/25
Kim JungNey GinaFrone Megan NHaley Jeremy SRamos Mark Louis FMirshahi Uyenlinh LAstiazaran-Symonds EstebanShandrina MariyaUrban GretchenRao H ShankerStahl Richard CGolden AliciaYohe Marielle EGross Andrea MDing YiCarey David JGelb Bruce DStewart Douglas R