Suchitha G P, Balaya Rex Devasahayam Arokia, Raju Rajesh, Keshava Prasad T S, Dagamajalu Shobha
Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Mangalore, Karnataka, 575018, India.
Centre for Integrative Omics Data Science, Yenepoya (Deemed to Be University), Mangalore, Karnataka, 575018, India.
J Cell Commun Signal. 2023 Sep;17(3):1097-1104. doi: 10.1007/s12079-023-00739-w. Epub 2023 Mar 21.
Cytoskeleton-associated protein 4 (CKAP4) is a non-glycosylated type II transmembrane protein that serves as a cell surface-activated receptor. It is expressed primarily in the plasma membranes of bladder epithelial cells, type II alveolar pneumocytes, and vascular smooth muscle cells. CKAP4 is involved in various biological activities including cell proliferation, cell migration, keratinocyte differentiation, glycogenesis, fibrosis, thymic development, cardiogenesis, neuronal apoptosis, and cancer. CKAP4 has been described as a pro-tumor molecule that regulates the progression of various cancers, including lung cancer, breast cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, cervical cancer, oral cancer, bladder cancer, cholangiocarcinoma, pancreatic cancer, myeloma, renal cell carcinoma, melanoma, squamous cell carcinoma, colorectal cancer, and osteosarcoma. CKAP4 and its isoform bind to DKK1 or DKK3 (Dickkopf proteins) or antiproliferative factor (APF) and regulates several downstream signaling cascades. The CKAP4 complex plays a crucial role in regulating the signaling pathways including PI3K/AKT and MAPK1/3. Recently, CKAP4 has been recognized as a potential target for cancer therapy. Due to its biomedical importance, we integrated a network map of CKAP4. The available literature on CKAP4 signaling was manually curated according to the NetPath annotation criteria. The consolidated pathway map comprises 41 activation/inhibition events, 21 catalysis events, 35 molecular associations, 134 gene regulation events, 83 types of protein expression, and six protein translocation events. CKAP4 signaling pathway map data is freely accessible through the WikiPathways Database ( https://www.wikipathways.org/index.php/Pathway:WP5322 ). Generation of CKAP4 signaling pathway map.
细胞骨架相关蛋白4(CKAP4)是一种非糖基化的II型跨膜蛋白,作为细胞表面激活受体发挥作用。它主要在膀胱上皮细胞、II型肺泡上皮细胞和血管平滑肌细胞的质膜中表达。CKAP4参与多种生物学活动,包括细胞增殖、细胞迁移、角质形成细胞分化、糖原生成、纤维化、胸腺发育、心脏发生、神经元凋亡和癌症。CKAP4被描述为一种促肿瘤分子,可调节包括肺癌、乳腺癌、食管鳞状细胞癌、肝细胞癌、宫颈癌、口腔癌、膀胱癌、胆管癌、胰腺癌、骨髓瘤、肾细胞癌、黑色素瘤、鳞状细胞癌、结直肠癌和骨肉瘤在内的多种癌症的进展。CKAP4及其异构体与DKK1或DKK3(Dickkopf蛋白)或抗增殖因子(APF)结合,并调节多个下游信号级联反应。CKAP4复合物在调节包括PI3K/AKT和MAPK1/3在内的信号通路中起关键作用。最近,CKAP4已被认为是癌症治疗的潜在靶点。由于其在生物医学方面的重要性,我们整合了CKAP4的网络图谱。根据NetPath注释标准,手动整理了关于CKAP4信号传导的现有文献。整合后的通路图谱包括41个激活/抑制事件、21个催化事件、35个分子关联、134个基因调控事件、83种蛋白质表达类型和6个蛋白质转位事件。CKAP4信号通路图谱数据可通过WikiPathways数据库(https://www.wikipathways.org/index.php/Pathway:WP5322)免费获取。CKAP4信号通路图谱的生成。