Artemin (ARTN) is a member of the glial cell line‐derived neurotrophic factor (GDNF) family ligands (GFLs), which encompasses family members, GDNF, neurturin (NRTN) and persephin (PSPN). ARTN is also referred to as Enovin or Neublastin, and bears structural characteristics of the TGF‐β superfamily. ARTN contains a dibasic cleavage site (RXXR) that is predicted to be cleaved by furin to yield a carboxy‐terminal 113 amino acid mature form. ARTN binds preferentially to receptor GFRα3, coupled to a receptor tyrosine kinase RET, forming a signalling complex for the regulation of intracellular pathways that affect diverse outcomes of nervous system development and homoeostasis. Standard signalling cascades activated by GFLs via RET include the phosphorylation of mitogen‐activated protein kinase or MAPK (p‐ERK, p‐p38 and p‐JNK), PI3K‐AKT and Src. Neural cell adhesion molecule (NCAM) is an alternative signalling receptor for ARTN in the presence of GFRα1, leading to activation of Fyn and FAK. Further, ARTN also interacts with heparan sulphate proteoglycan syndecan‐3 and mediates non‐RET signalling via activation of Src kinases. This review discusses the role of ARTN in spinal cord injury, neuropathic pain and other neurological disorders. Additionally, ARTN plays a role in non‐neuron tissues, such as the formation of Peyer's patch‐like structures in the lymphoid tissue of the gut. The emerging role of ARTN in cancers and therapeutic resistance to cancers is also explored. Further research is necessary to determine the function of ARTN in a tissue‐specific manner, including its signalling mechanisms, in order to improve the therapeutic potential of ARTN in human diseases.

中文翻译：

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神经胶质细胞系衍生神经营养因子家族成员artemin在神经系统疾病和癌症中的作用

Artemin (ARTN) 是神经胶质细胞系衍生的神经营养因子 (GDNF) 家族配体 (GFL) 的成员，包括家族成员 GDNF、neurturin (NRTN) 和 persephin (PSPN)。ARTN 也称为 Enovin 或 Neublastin，具有 TGF-β 超家族的结构特征。ARTN 包含一个二碱基切割位点 (RXXR)，预计该位点会被弗林蛋白酶切割以产生羧基末端 113 个氨基酸的成熟形式。ARTN 优先与受体 GFRα3 结合，与受体酪氨酸激酶 RET 偶联，形成信号复合物，用于调节影响神经系统发育和稳态的多种结果的细胞内通路。GFL 通过 RET 激活的标准信号级联包括丝裂原活化蛋白激酶或 MAPK（p-ERK、p-p38 和 p-JNK）、PI3K-AKT 和 Src 的磷酸化。在 GFRα1 存在下，神经细胞粘附分子 (NCAM) 是 ARTN 的替代信号受体，可导致 Fyn 和 FAK 的激活。此外，ARTN 还与硫酸乙酰肝素蛋白多糖 syndecan-3 相互作用，并通过激活 Src 激酶介导非 RET 信号传导。本综述讨论了 ARTN 在脊髓损伤、神经性疼痛和其他神经系统疾病中的作用。此外，ARTN 在非神经元组织中也发挥作用，例如在肠道淋巴组织中形成 Peyer 斑块状结构。还探讨了 ARTN 在癌症中的新兴作用和对癌症的治疗抗性。需要进一步研究以组织特异性方式确定 ARTN 的功能，包括其信号传导机制，以提高 ARTN 在人类疾病中的治疗潜力。