EGF信号:追踪癌症的路径-null-资讯-生物在线

EGF信号:追踪癌症的路径

作者:上海阿拉丁生化科技股份有限公司 2022-12-02T15:33 (访问量:792)

表皮生长因子(EGF)家族是一组结构相关的蛋白质,通过靶细胞上的酪氨酸激酶受体调节细胞增殖、迁移和分化。EGF受体有一个细胞质酪氨酸激酶结构域,一个跨膜结构域和一个与EGF结合的细胞外结构域。配体与EGF受体结合导致其二聚、自磷酸化和激活。一旦被激活,EGF受体通过几个蛋白质的磷酸化传递细胞内信号。


Ras被EGF受体激活是EGF信号转导的重要组成部分。鸟嘌呤核苷酸交换因子SOS激活Ras, Ras进而触发丝裂原激活蛋白(MAP)激酶通路。MAP激酶磷酸化转录因子,如激活蛋白1(AP-1;Fos-Jun二聚体)和Elk-1,导致细胞生长和发育。EGFR对Janus激酶(JAK)的磷酸化导致转录蛋白信号换能器和激活器(STATs)的激活,最终导致细胞的生长和分化。EGF信号的另一个关键方面涉及磷脂酶c - γ1 (PLCγ1),它将PIP2裂解为IP3和DAG。IP3的产生导致内质网钙的释放,而DAG促进蛋白激酶C (PKC)的激活。PKC反过来磷酸化并激活转录因子Elk-1,导致细胞增殖。已知EGFR的突变影响其表达或活性,这使EGFR成为重要的药物靶点。


该通路强调了EGF信号转导的重要组成部分。


几个重要的表皮生长因子信号通路




参考文献

1. Corbalan-Garcia S, Margarit SM, Galron D, Yang S, Bar-Sagi D.1998. Regulation of Sos Activity by Intramolecular Interactions. Mol. Cell. Biol.. 18(2):880-886. https://doi.org/10.1128/mcb.18.2.880

2. Russell M, Lange-Carter CA, Johnson GL. 1995. Direct Interaction between Ras and the Kinase Domain of Mitogen-activated Protein Kinase Kinase Kinase (MEKK1). Journal of Biological Chemistry. 270(20):11757-11760. https://doi.org/10.1074/jbc.270.20.11757

3. Ackerman P, Glover CV, Osheroff N. 1990. Stimulation of casein kinase II by epidermal growth factor: relationship between the physiological activity of the kinase and the phosphorylation state of its beta subunit..Proceedings of the National Academy of Sciences. 87(2):821-825. https://doi.org/10.1073/pnas.87.2.821

4. Andl CD, Mizushima T, Oyama K, Bowser M, Nakagawa H, Rustgi AK. 2004. EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes. American Journal of Physiology-Gastrointestinal and Liver Physiology. 287(6):G1227-G1237. https://doi.org/10.1152/ajpgi.00253.2004

5. Baker SJ, Kerppola TK, Luk D, Vandenberg MT, Marshak DR, Curran T, Abate C. 1992. Jun is phosphorylated by several protein kinases at the same sites that are modified in serum-stimulated fibroblasts.. Mol. Cell. Biol.. 12(10):4694-4705. https://doi.org/10.1128/mcb.12.10.4694

6. Takekawa M, Tatebayashi K, Saito H. 2005. Conserved Docking Site Is Essential for Activation of Mammalian MAP Kinase Kinases by Specific MAP Kinase Kinase Kinases. Molecular Cell. 18(3):295-306. https://doi.org/10.1016/j.molcel.2005.04.001

7. Chong M, Barritt G, Crouch M. 2004. Insulin potentiates EGFR activation and signaling in fibroblasts. Biochemical and Biophysical Research Communications. 322(2):535-541. https://doi.org/10.1016/j.bbrc.2004.07.150

8. Krug AW, Schuster C, Gassner B, Freudinger R, Mildenberger S, Troppmair J, Gekle M. 2002. Human Epidermal Growth Factor Receptor-1 Expression Renders Chinese Hamster Ovary Cells Sensitive to Alternative Aldosterone Signaling. Journal of Biological Chemistry. 277(48):45892-45897. https://doi.org/10.1074/jbc.m208851200

9. Lim CP, Cao X. 1999. Serine Phosphorylation and Negative Regulation of Stat3 by JNK. Journal of Biological Chemistry. 274(43):31055-31061. https://doi.org/10.1074/jbc.274.43.31055

10. Diakonova M, Payrastre B, van Velzen AG, Hage W, van Bergen en Henegouwen PM, Boonstra J, Cremers F, Humbel B. 1995. Epidermal growth factor induces rapid and transient association of phospholipase C-gamma 1 with EGF-receptor and filamentous actin at membrane ruffes of A431 cells.. J Cell Sci..(108):2499–2509.

11. Eldar H, Zisman Y, Ullrich A, Livneh E. 1990. Overexpression of protein kinase C alpha-subtype in Swiss/3T3 fibroblasts causes loss of both high and low affinity receptor numbers for epidermal growth factor.. Journal of Biological Chemistry. 265(22):13290-13296. https://doi.org/10.1016/s0021-9258(19)38297-3

12. Weston CR, Wong A, Hall JP, Goad MEP, Flavell RA, Davis RJ. 2004. The c-Jun NH2-terminal kinase is essential for epidermal growth factor expression during epidermal morphogenesis. Proceedings of the National Academy of Sciences. 101(39):14114-14119. https://doi.org/10.1073/pnas.0406061101

13. Carpenter G, Cohen S. 1990. Epidermal growth factor.. Journal of Biological Chemistry. 265(14):7709-7712. https://doi.org/10.1016/s0021-9258(19)38983-5

14. Hu, Bowtell D. 1996. Sos1 rapidly associates with Grb2 and is hypophosphorylated when complexed with the EGF receptor after EGF stimulation. Oncogene.. 12(9):1865–72.

15. Ueno H, Sasaki K, Miyagawa K, Honda H, Mitani K, Yazaki Y, Hirai H. 1997. Antisense Repression of Proto-oncogene c-Cbl Enhances Activation of the JAK-STAT Pathway but Not the Ras Pathway in Epidermal Growth Factor Receptor Signaling. Journal of Biological Chemistry. 272(13):8739-8743. https://doi.org/10.1074/jbc.272.13.8739

16. Cummins AB, Palmer C, Mossman BT, Taatjes DJ. 2003. Persistent Localization of Activated Extracellular Signal-Regulated Kinases (ERK1/2) Is Epithelial Cell-Specific in an Inhalation Model of Asbestosis. The American Journal of Pathology. 162(3):713-720. https://doi.org/10.1016/s0002-9440(10)63867-9

17. Yoshikawa S, Tanimura T, Miyawaki A, Nakamura M, Yuzaki M, Furuichi T, Mikoshiba K. 1992. Molecular cloning and characterization of the inositol 1,4,5-trisphosphate receptor in Drosophila melanogaster.. Journal of Biological Chemistry. 267(23):16613-16619. https://doi.org/10.1016/s0021-9258(18)42047-9

18. Mahimainathan L, Ghosh-Choudhury N, Venkatesan BA, Danda RS, Choudhury GG. 2005. EGF stimulates mesangial cell mitogenesis via PI3-kinase-mediated MAPK-dependent and AKT kinase-independent manner: involvement of c-fos and p27Kip1. American Journal of Physiology-Renal Physiology. 289(1):F72-F82. https://doi.org/10.1152/ajprenal.00277.2004

19. Xia Y, Makris C, Su B, Li E, Yang J, Nemerow GR, Karin M. 2000. MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration. Proceedings of the National Academy of Sciences. 97(10):5243-5248. https://doi.org/10.1073/pnas.97.10.5243

20. Chen D, Davis JS. 2003. Epidermal growth factor induces c-fos and c-jun mRNA via Raf-1/MEK1/ERK-dependent and -independent pathways in bovine luteal cells. Molecular and Cellular Endocrinology. 200(1-2):141-154. https://doi.org/10.1016/s0303-7207(02)00379-9

上海阿拉丁生化科技股份有限公司 商家主页

地 址: 上海市新金桥路36号财富中心16楼

联系人: 阿博士

电 话: 400-620-6333

传 真: 021-50323701

Email:market@aladdin-e.com

相关咨询

【阿拉丁】蛋白质&抗体秋季特惠活动来袭! (2024-11-14T00:00 浏览数:3064)

【阿拉丁】细胞的营养“奶酪”——L-酪氨酸 (2024-10-14T00:00 浏览数:7815)

【阿拉丁】右旋糖酐:生物医学多功能多糖 (2024-09-12T00:00 浏览数:10403)

【阿拉丁】抗体应用和技术 (2024-09-06T00:00 浏览数:11849)

科研开学季,【阿拉丁】生物满赠礼! (2024-08-30T00:00 浏览数:12510)

【阿拉丁】BrdU染色方案 (2024-08-21T00:00 浏览数:12681)

【阿拉丁】细菌的外衣——脂多糖LPS (暂无发布时间 浏览数:16397)

【阿拉丁】三甲胺硼烷/硼烷三甲胺复合物 (暂无发布时间 浏览数:13237)

【阿拉丁】使用ICP MS结合氩气稀释(AGD)对锂盐进行元素分析 (2024-07-05T00:00 浏览数:20001)

【阿拉丁】EBL-3183的工艺之路:从吲哚到临床前抑制剂 (暂无发布时间 浏览数:20241)

ADVERTISEMENT