Protein Kinase Classification: TK/Ret※ Ret family introduction RET kinase is a receptor tyrosine kinase encoded by RET gene. Structure analysis shows that RET consist of an extracellular region and an intracellular region. The extracellular contains four cadherin-linke domains, a cysteine-rich region and a membrane-spanning region (1). The intracellular region contains a tyrosine kinase domain. Binding of Ca2+ to cadherin-linke domain lead to the RET autophosphorylation of intracellular tyrosine sites which will act as docking sites for SH2 and PTB domain-containing protein and subsequently trigger the downstream signaling pathway, including RAS/MAPK/ERK1,2, PI3K/Akt, JNK, STAT3, SRC, ERK5 and p38SAPK (2).
Reference
1. Morandi, A., Plaza-Menacho, I. and Isacke, C.M. (2011) RET in breast cancer: functional and therapeutic implications. Trends Mol Med, 17, 149-157. PMID: 21454698
2. Plaza-Menacho, I., Morandi, A., Mologni, L., Boender, P., Gambacorti-Passerini, C., Magee, A.I., Hofstra, R.M., Knowles, P., McDonald, N.Q. and Isacke, C.M. (2011) Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET-FAK transactivation mechanism. J Biol Chem, 286, 17292-17302. PMID: 21251878
TK Ret in eukaryotes:
1. Morandi, A., Plaza-Menacho, I. and Isacke, C.M. (2011) RET in breast cancer: functional and therapeutic implications. Trends Mol Med, 17, 149-157. PMID: 21454698
2. Plaza-Menacho, I., Morandi, A., Mologni, L., Boender, P., Gambacorti-Passerini, C., Magee, A.I., Hofstra, R.M., Knowles, P., McDonald, N.Q. and Isacke, C.M. (2011) Focal adhesion kinase (FAK) binds RET kinase via its FERM domain, priming a direct and reciprocal RET-FAK transactivation mechanism. J Biol Chem, 286, 17292-17302. PMID: 21251878
TK Ret in eukaryotes: