| 纯度 | >85%SDS-PAGE. |
| 种属 | Human |
| 靶点 | RET |
| Uniprot No | P07949 |
| 内毒素 | < 0.01EU/μg |
| 表达宿主 | E.coli |
| 表达区间 | 658-1114aa |
| 氨基酸序列 | HCYHKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVD AFKILEDPKWEFPRKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAV KMLKENASPSELRDLLSEFNVLKQVNHPHVIKLYGACSQDGPLLLIVEYA KYGSLRGFLRESRKVGPGYLGSGGSRNSSSLDHPDERALTMGDLISFAWQ ISQGMQYLAEMKLVHRDLAARNILVAEGRKMKISDFGLSRDVYEEDSYVK RSQGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPP ERLFNLLKTGHRMERPDNCSEEMYRLMLQCWKQEPDKRPVFADISKDLEK MMVKRRDYLDLAASTPSDSLIYDDGLSEEETPLVDCNNAPLPRALPSTWI ENKLYGMSDPNWPGESPVPLTRADGTNTGFPRYPNDSVYANWMLSPSAAK LMDTFDS |
| 预测分子量 | 74 kDa |
| 蛋白标签 | His tag N-Terminus |
| 缓冲液 | PBS, pH7.4, containing 0.01% SKL, 1mM DTT, 5% Trehalose and Proclin300. |
| 稳定性 & 储存条件 | Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months. |
| 复溶 | Always centrifuge tubes before opening.Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles. |
以下是关于RET重组蛋白的3-4篇代表性文献的简要总结：
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1. **文献名称**：*Identification of RET gene mutations and activation mechanisms in human cancers*
**作者**：Mulligan LM, et al.
**摘要**：该研究首次克隆了RET原癌基因，并揭示了其激活突变(如重组、点突变)与多发性内分泌瘤(MEN2)和甲状腺髓样癌(MTC)的关联，阐明了RET信号通路异常在肿瘤发生中的作用。
2. **文献名称**：*Selective RET kinase inhibition for patients with RET-altered cancers*
**作者**：Drilon A, et al.
**摘要**：该临床试验(LOXO-292.即Selpercatinib)验证了选择性RET抑制剂对RET融合阳性非小细胞肺癌(NSCLC)和RET突变甲状腺癌患者的显著疗效，推动了靶向治疗的发展。
3. **文献名称**：*Structural basis of RET transmembrane domain activation by oncogenic mutations*
**作者**：Plenker D, et al.
**摘要**：通过冷冻电镜解析了RET跨膜结构域的激活机制，发现致癌性重组(如CCDC6-RET)导致受体二聚化异常，为设计小分子抑制剂提供了结构基础。
4. **文献名称**：*RET fusions in solid tumors: A diagnostic and therapeutic target*
**作者**：Subbiah V, et al.
**摘要**：系统总结了RET融合在肺癌、甲状腺癌、胰腺癌等实体瘤中的发生率及分子特征，强调多激酶抑制剂(如Cabozantinib)和新型RET特异性抑制剂的应用前景。
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这些文献涵盖了RET重组蛋白的致癌机制、靶向治疗及结构生物学研究，是领域内的重要参考。
RET (REarranged during Transfection) is a receptor tyrosine kinase critical for cell signaling, embryonic development, and tissue homeostasis. Discovered in 1985 via its oncogenic rearrangement in papillary thyroid carcinoma, RET encodes a single-pass transmembrane protein with extracellular cadherin-like domains, a cysteine-rich region, and an intracellular tyrosine kinase domain. It primarily binds glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) through a co-receptor complex involving GDNF family receptor α (GFRα), triggering dimerization, autophosphorylation, and downstream signaling cascades (e.g., RAS/MAPK, PI3K/AKT, JNK). These pathways regulate cell survival, proliferation, differentiation, and migration.
Dysregulated RET signaling is implicated in cancers and developmental disorders. Activating mutations (e.g., MEN2-associated mutations) or chromosomal rearrangements (e.g., RET fusions in lung/thyroid cancers) drive oncogenesis by conferring ligand-independent kinase activation. Conversely, inactivating mutations cause Hirschsprung’s disease, characterized by enteric nervous system defects.
Recombinant RET proteins, produced via bacterial, mammalian, or insect cell systems, enable functional and structural studies. They serve as tools to investigate mutation effects, screen kinase inhibitors (e.g., vandetanib, selpercatinib), and develop diagnostic/therapeutic antibodies. Crystallography studies using recombinant RET kinase domains have informed structure-based drug design, improving inhibitor specificity against resistance mutations. Additionally, RET fusion proteins expressed in model systems help validate oncogenic mechanisms and therapeutic targets. The clinical success of RET-targeted therapies underscores the importance of recombinant proteins in elucidating RET biology and advancing precision oncology.
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