产品描述:
ALK was a novel receptor tyrosine kinase (RTK), having an extracellular ligand-binding domain, a transmembrane domain, and an intracellular tyrosine kinase domain. While the tyrosine kinase domain of human ALK shares a high degree of similarity with that of the insulin receptor, its extracellular domain is unique among the RTK family in containing two MAM domains (meprin, A5 protein and receptor protein tyrosine phosphatase mu), an LDLa domain (low-density lipoprotein receptor class A) and a glycine-rich region. Following binding of the ligand, the full-length receptor ALK dimerizes, changes conformation, and autoactivates its own kinase domain, which in turn phosphorylates other ALK receptors in trans on specific tyrosine amino acid residues. ALK phosphorylated residues serve as binding sites for the recruitment of several adaptor and other cellular proteins, such as GRB2, IRS1, Shc, Src, FRS2, PTPN11/Shp2, PLCgamma, PI3K and NF1. Other reported downstream ALK targets include FOXO3a, CDKN1B/p27kip, cyclin D2, NIPA, RAC1, CDC42, p130CAS, SHP1 and PIKFYVE. Phosphorylated ALK activates multiple downstream signal transduction pathways, including MAPK-ERK, PI3K-AKT, PLCgamma, CRKL-C3G and JAK-STAT. The receptor ALK plays a pivotal role in cellular communication and in the normal development and function of the nervous system. Oncogenic ALK is expressed and used as a marker in anaplastic large-cell lymphomas (ALCLs) and non-small-cell lung cancer (NSCLC).