The role of the receptor complex and the cofactors in IGSF10 signaling

受体复合物和辅助因子在 IGSF10 信号传导中的作用

• 批准号: 10728450
• 负责人: YUZURU SHIIO
• 金额: $ 35.46万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-07 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10728450
• 关键词: Basic Science; Binding; Biological; Biological Process; Biology; C-terminal; Cell Line; Cell Proliferation; Cell Surface Proteins; Cell Surface Receptors; Cell model; Cells; Cleidocranial Dysplasia; Collaborations; Complex; Cysteine-Rich Domain; Delayed Puberty; Ewings sarcoma; Foundations; Frameshift Mutation; Future; Gene Expression; Glioma; Gonadotropin Hormone Releasing Hormone; Growth; Human; Immunoglobulins; Inherited; Knowledge; Leucine-Rich Repeat; Ligands; Link; Malignant neoplasm of lung; Mediating; Microglia; Molecular; Mus; Mutation; N-terminal; National Institute of Neurological Disorders and Stroke; Neurons; Pathologic; Pathologic Processes; Pathway interactions; Phenocopy; Physiological; Pituitary Hormones; Play; Protein Secretion; Protein Tyrosine Kinase; Proteomics; RET inhibition; Research; Role; Signal Pathway; Signal Transduction; Structure; System; Testing; Therapeutic; Tissues; United States National Institutes of Health; Variant; cofactor; hormone deficiency; immunoglobulin receptor; inhibitor; kinase inhibitor; knock-down; malignant breast neoplasm; member; migration; mutant; novel; olfactomedin; prevent; protein function; proto-oncogene protein c-ret; receptor; skeletal disorder; transcriptome sequencing; tumor

Immunoglobulin superfamily member 10 (IGSF10) is a large, secreted protein implicated in multiple biological and pathological processes: IGSF10 mutations are associated with hereditary delayed puberty. Low IGSF10 expression is linked to more aggressive lung and breast cancers. A frameshift mutation in IGSF10 was found in a case of a hereditary skeletal disorder, Cleidocranial Dysplasia. IGSF10 A1672T variant was found in combined pituitary hormone deficiency. However, the mechanism of action of IGSF10 is unknown. The applicant’s group identified the cell surface receptor for IGSF10 and the downstream signaling pathway regulated by IGSF10. They also identified a putative co-receptor and a secreted co-factor for IGSF10. This project is directed towards understanding the roles of the receptor complex and the cofactors in IGSF10 signaling. The successful completion of the project will uncover the molecular mechanisms and the biological roles of the novel signaling pathway mediated by IGSF10. The knowledge gained from this project will lay the foundation for understanding the physiological roles of this novel signaling pathway as well as the pathological conditions associated with the dysregulation of this pathway.

免疫球蛋白超家族成员10（IGSF10）是一种大型的，分泌的蛋白质，隐含在多种生物学中 和病理过程：IGSF10突变与山神父延迟青春期有关。低IGSF10 表达与更具侵略性的肺和乳腺癌有关。在IGSF10中发现了一个移码突变 一种遗传性骨骼疾病的病例，是克氏氏菌发育不良。在合并中发现了IGSF10 A1672T变体 垂体马酮缺乏症。但是，IGSF10的作用机理尚不清楚。 申请人组确定了IGSF10和下游信号通路的细胞表面受体 由IGSF10调节。他们还确定了一个假定的共核能和IGSF10的分泌共同因素。这 项目旨在了解接收器复合物和IGSF10中的辅助因子的作用 信号。该项目的成功完成将揭示分子机制和生物学 IGSF10介导的新型信号通路的作用。从这个项目中获得的知识将为 理解这种新颖信号通路的物理作用以及病理的基础 与该途径失调相关的条件。