Sandbox Reserved 1726: Difference between revisions

Anaplastic Lymphoma Kinase (ALK) is a [https://en.wikipedia.org/wiki/Transmembrane_protein transmembrane] receptor and a member of the family of [https://proteopedia.org/wiki/index.php/Receptor_tyrosine_kinases Receptor Tyrosine Kinases (RTKs)]. RTKs are a family of biomolecules that are primarily responsible for biosignaling pathways such as the insulin signaling pathway. ALK was identified as a novel tyrosine phosphoprotein in 1994 in an analysis of [https://lymphoma.org/aboutlymphoma/nhl/alcl/ Anaplastic Large-Cell Lymphoma], the protein's namesake. A full analysis and characterization of ALK was completed in 1997, properly identifying it as a RTK, and linking it closely to [https://en.wikipedia.org/wiki/Leukocyte_receptor_tyrosine_kinase Leukocyte Tyrosine Kinase] (LTK).  

ALK is a close homolog of LTK, and together these two homologues constitute a subgroup within the superfamily of [https://proteopedia.org/wiki/index.php/Insulin_receptor insulin receptors] (IR). ALK is composed of 1620 amino acids, with three primary domains, the extracellular domain, the transmembrane domain, and the intracellular domain. [[Image:ALK Structure Overview.PNG|300 px|right|thumb|Figure 1. Overview of Anaplastic Lymphoma Kinase Structure]] The intracellular tyrosine kinase domain ranges from residues 1116-1392, and features the [https://en.wikipedia.org/wiki/C-terminus C-terminal end] (Figure 1). The [https://en.wikipedia.org/wiki/Transmembrane_domain transmembrane helical domain] (TMH) bridges the gap between the intracellular and extracellular regions from residues 1039-1116. The final section of ALK is the extracellular region, which spans from residues 1025 to 1, and contains 8 domains. Of these 8 domains, two regions of the extracellular region can be found; one containing the ligand-binding site of the protein, and another lesser-known subregion. This lesser-known subregion contains 4 domains from residues 1-626; an [https://en.wikipedia.org/wiki/N-terminus N-terminal Region] (NTR), two [https://en.wikipedia.org/wiki/Meprin_A meprin–A-5] protein–receptor protein tyrosine phosphatase μ (MAM), and a [https://en.wikipedia.org/wiki/Low-density_lipoprotein low-density lipoprotein] receptor class A (LDL) domain sandwiched between the two MAM domains. The presence of an LDL domain sandwiched by two MAM domains is a unique feature that ALK does not share with other RTKs. The purpose behind this unique difference is still unclear. The ligand-binding extracellular subregion is the most well-characterized of the two subregions, containing 4 distinct domains from residues 673-1025; a triple helix bundle (THB) domain, a glycine-rich domain (GlyR) that is also referred to as the poly-Glycine domain, a tumor necrosis factor-like (TNF-like), and an epidermal growth factor-like domain (EGF-like). All four domains of this subregion of the extracellular region contribute to ligand-binding <ref name ="Huang" />

Mutations in Anaplastic Lymphoma Kinase can produce oncogenic activity and are a leading factor in the development of some pediatric neuroblastoma cases<ref name="Borenas" />. 8-10% of primary neuroblastoma patients are ALK positive<ref name="Borenas" /> suggesting that ALK overstimulation is a primary factor in propagating the growth of neuroblastoma. This overstimulation of ALK works in concert with the neural MYC oncogene, and uses the ALKAL2 ligand. Tyrosine kinase inhibitors are proposed to inhibit the growth of further neuroblastoma cells, creating a potential pathway of treatment<ref name="Borenas" />  

</StructureSection>.