药物介导的 MET 激活抑制
中文名称
通路描述
MET 受体酪氨酸激酶（RTK）是一种原癌基因，通过基因扩增和/或激活突变被频繁异常激活，导致对 HGF 刺激或 HGF 独立激活的敏感性增加。致癌 MET 激活可作为恶性转化的主要机制，也可作为靶向相关 RTK 药物（如 EGFR）治疗抵抗的次要机制。针对 MET 的抗癌药物，无论是重组单克隆抗体（MAbs）还是小酪氨酸激酶抑制剂（TKIs），在作为原发性 MET 激活实体瘤的一线治疗药物，或作为靶向其他 RTK 药物治疗获得性 MET 介导抵抗的实体瘤二线治疗药物方面显示出前景（综述：Comoglio 等，2018）。
英文描述
Translation of Replicase and Assembly of the Replication Transcription Complex This COVID-19 pathway has been created by a combination of computational inference from SARS-CoV-1 data (https://reactome.org/documentation/inferred-events) and manual curation, as described in the summation for the overall SARS-CoV-2 infection pathway.
After entry and uncoating, the genomic RNA serves as a transcript to allow cap dependent translation of ORF1a to produce polyprotein pp1a. A slippery sequence and an RNA pseudoknot near the end of ORF1a enable 25 - 30% of ribosomes to undergo -1 frameshifting, to continue translation of ORF1b to produce a longer polyprotein pp1ab. Autoproteolytic cleavage of pp1a and pp1ab generates 15-16 nonstructural proteins (nsps) with various functions. RNA dependent RNA polymerase (RdRP) activity is encoded in nsp12, and papain like protease (PLPro) and main protease (Mpro) activities are encoded in nsp3 and nsp5, respectively. nsp3, 4, and 6 induce rearrangement of the cellular membrane to form double membrane vesicles (DMVs) where the coronavirus replication transcription complex (RTC) is assembled and anchored.
Programmed ribosomal frameshifting (PRF) may be regulated by viral or host factors in addition to viral RNA secondary structures. For example, PRF in the related arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) is transactivated by the viral protein nsp1, which interacts with the PRF signal via a putative RNA binding motif. A host RNA-binding protein called annexin A2 (ANXA2) binds the pseudoknot structure in the IBV genome. Host factors in the early secretory pathway appear to be involved in DMV formation and RTC assembly: Golgi specific brefeldin A resistance guanine nucleotide exchange factor 1 (GBF1) and its effector ADP ribosylation factor 1 (ARF1) are both required for normal DMV formation and efficient RNA replication of mouse hepatitis virus (MHV), a prototypic betacoronavirus that infects mice (Fung & Liu 2019).
After entry and uncoating, the genomic RNA serves as a transcript to allow cap dependent translation of ORF1a to produce polyprotein pp1a. A slippery sequence and an RNA pseudoknot near the end of ORF1a enable 25 - 30% of ribosomes to undergo -1 frameshifting, to continue translation of ORF1b to produce a longer polyprotein pp1ab. Autoproteolytic cleavage of pp1a and pp1ab generates 15-16 nonstructural proteins (nsps) with various functions. RNA dependent RNA polymerase (RdRP) activity is encoded in nsp12, and papain like protease (PLPro) and main protease (Mpro) activities are encoded in nsp3 and nsp5, respectively. nsp3, 4, and 6 induce rearrangement of the cellular membrane to form double membrane vesicles (DMVs) where the coronavirus replication transcription complex (RTC) is assembled and anchored.
Programmed ribosomal frameshifting (PRF) may be regulated by viral or host factors in addition to viral RNA secondary structures. For example, PRF in the related arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) is transactivated by the viral protein nsp1, which interacts with the PRF signal via a putative RNA binding motif. A host RNA-binding protein called annexin A2 (ANXA2) binds the pseudoknot structure in the IBV genome. Host factors in the early secretory pathway appear to be involved in DMV formation and RTC assembly: Golgi specific brefeldin A resistance guanine nucleotide exchange factor 1 (GBF1) and its effector ADP ribosylation factor 1 (ARF1) are both required for normal DMV formation and efficient RNA replication of mouse hepatitis virus (MHV), a prototypic betacoronavirus that infects mice (Fung & Liu 2019).
所含基因
13 个基因