文献类型：期刊文献

英文题名：AKAP12 as a signal-compartmentalizing Hub across diseases: Context-dependent functions and translational potential

作者：Tian, Jiao[1];Lu, Yuyuan[1];Wu, Tao[1,3];Ma, Ruiling[1];Li, Wenjun[1];Sheng, Lufan[1];Xiao, Wenmiao[1];Zhang, Lingna[1];Wang, Yiyuan[1];Wang, Liqiang[2];Jin, Penghui[2];Li, Bin[1];Gu, Yuanhui[2,3];Yi, Lin[1,3]

第一作者：Tian, Jiao

通信作者：Gu, YH[1];Yi, L[1]

机构：[1]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Prov Hosp, Dept Gen Surg, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Prov Hosp, Dept Gen Surg, Lanzhou 730000, Gansu, Peoples R China.

年份：2026

卷号：148

外文期刊名：CELLULAR SIGNALLING

收录：;Scopus(收录号：2-s2.0-105046756244);WOS:【SCI-EXPANDED(收录号:WOS:001848480600001)】；

基金：Science and Technology Support Program Project of Chengguan District, Lanzhou City, No. 2025-zc-32; Project on Scientific Research of Traditional Chinese Medicine in Gansu Province, No. GZKZ-2025-56; Gansu Provincial Department of Science and Technology, Key Research and Development Program Project, No. 26YFFA028; General Program of the Joint Scientific Research Fund, No. 23JRRA1521; Department of Science and Technology of Gansu Province and Natural Science Foundation of Gansu Province, No. 24JRRA590; Gansu Provincial Department of Education University Teacher Innovation Fund, No. 2026-A112; Youth Science and Technology Fund of Gansu Provincial Science and Technology Program, No. 25JRRA935.

语种：英文

外文关键词：AKAP12; Signal compartmentalization; Tumor microenvironment; Endothelial barrier; Neuroinflammation; Fibrosis; Translational medicine

摘要：A-kinase anchoring protein 12 (AKAP12; Gravin/SSeCKS) is a multidomain scaffold that coordinates spatially restricted signaling rather than acting as a single linear effector. By organizing protein kinase A (PKA), protein kinase C (PKC), phosphodiesterases (PDEs), proto-oncogenic non-receptor tyrosine kinase (Src)-related modules, and cytoskeleton- or adhesion-associated proteins within local signaling microdomains, AKAP12 regulates kinase output, PDE-dependent cyclic adenosine monophosphate (cAMP) gradients, cytoskeletal remodeling, cell migration, barrier integrity, inflammatory activation, fibrosis, and tissue repair. However, AKAP12-related evidence remains dispersed across oncology, cardiovascular biology, neurovascular research, and inflammatory disease. Its apparent protective or pathogenic roles are often interpreted without sufficient attention to cell type, isoform usage, post-translational modification, disease stage, or microenvironmental stress. This review integrates mechanistic and translational evidence for AKAP12 across cancer, cardiovascular and cerebrovascular disease, neurological disorders, and inflammation-related conditions. In malignant tumors, AKAP12 most often acts as a tumor suppressor by restraining oncogenic signaling, invasion, cytoskeletal reorganization, and metastatic niche formation; however, emerging studies also reveal pro-tumor functions in hypoxia-adapted melanoma, drug-resistant ovarian cancer, and AKAP12-positive cancer-associated fibroblast niches that drive macrophage-mediated immunosuppression. In the cardiovascular and neurovascular systems, AKAP12 shapes beta-adrenergic cAMP microdomains, PDE-dependent contractile responses, endothelial migration, blood-brain barrier stability, oligodendrocyte differentiation, and injury repair. In inflammatory and fibrotic disorders, AKAP12 links immune polarization, stromal remodeling, metabolic homeostasis, and organ repair. We propose that AKAP12 should be viewed as a dynamic signaling-interface module whose functional output depends on cellular origin, isoform context, and microenvironmental state. Future studies integrating single-cell and spatial omics, interactome proteomics, isoform-specific perturbation, organoid models, and precision delivery strategies will be essential to define when AKAP12 is protective, pathogenic, or therapeutically targetable.