内分泌及其他因子调节的钙重吸收
中文名称
通路描述
钙（Ca2+）对于许多生理功能至关重要，包括细胞内信号传导、神经兴奋性、肌肉收缩和骨形成。因此，其稳态通过协调肠道吸收、肾重吸收和骨吸收精细维持。在肾脏中，远曲小管（DCT）的晚期部分和连接小管（CNT）是进行主动 Ca2+ 转运的部位，并精确调节 Ca2+ 重吸收。Ca2+ 通过 TRPV5 进入细胞后，与钙调蛋白-D28K 结合，扩散至基底侧，并通过 NCX1 和 PMCA1b 被排出到血液。在尿液中，klotho 和组织激肽原（TK）增加了 TRPV5 的顶端丰度。在血液中，PTH、1,25(OH)2D3 和雌激素增加了钙通道、钙调蛋白和排出系统的转录和蛋白表达。
英文描述
Constitutive Signaling by EGFRvIII In glioblastoma, the most prevalent EGFR mutation, present in ~25% of tumors, is the deletion of the ligand binding domain of EGFR, accompanied with amplification of the mutated allele, which results in over-expression of the mutant protein known as EGFRvIII. EGFRvIII mutant is not able to bind a ligand, but dimerizes and autophosphorylates spontaneously and is therefore constitutively active (Fernandes et al. 2001). Point mutations in the extracellular domain of EGFR are also frequently found in glioblastoma, but ligand binding ability and responsiveness are preserved (Lee et al. 2006).
Similar to EGFR kinase domain mutants, EGFRvIII mutant needs to maintain association with the chaperone heat shock protein 90 (HSP90) for proper functioning (Shimamura et al. 2005, Lavictoire et al. 2003). CDC37 is a co-chaperone of HSP90 that acts as a scaffold and regulator of interaction between HSP90 and its protein kinase clients. CDC37 is frequently over-expressed in cancers involving mutant kinases and acts as an oncogene (Roe et al. 2004, reviewed by Gray Jr. et al. 2008).
Expression of EGFRvIII mutant results in aberrant activation of downstream signaling cascades, namely RAS/RAF/MAP kinase signaling and PI3K/AKT signaling, and possibly signaling by PLCG1, which leads to increased cell proliferation and survival, providing selective advantage to cancer cells that harbor EGFRvIII (Huang et al. 2007).
EGFRvIII mutant does not autophosorylate on the tyrosine residue Y1069 (i.e. Y1045 in the mature protein), a docking site for CBL, and is therefore unable to recruit CBL ubiquitin ligase, which enables it to escape degradation (Han et al. 2006)
Similar to EGFR kinase domain mutants, EGFRvIII mutant needs to maintain association with the chaperone heat shock protein 90 (HSP90) for proper functioning (Shimamura et al. 2005, Lavictoire et al. 2003). CDC37 is a co-chaperone of HSP90 that acts as a scaffold and regulator of interaction between HSP90 and its protein kinase clients. CDC37 is frequently over-expressed in cancers involving mutant kinases and acts as an oncogene (Roe et al. 2004, reviewed by Gray Jr. et al. 2008).
Expression of EGFRvIII mutant results in aberrant activation of downstream signaling cascades, namely RAS/RAF/MAP kinase signaling and PI3K/AKT signaling, and possibly signaling by PLCG1, which leads to increased cell proliferation and survival, providing selective advantage to cancer cells that harbor EGFRvIII (Huang et al. 2007).
EGFRvIII mutant does not autophosorylate on the tyrosine residue Y1069 (i.e. Y1045 in the mature protein), a docking site for CBL, and is therefore unable to recruit CBL ubiquitin ligase, which enables it to escape degradation (Han et al. 2006)
所含基因
10 个基因