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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). | 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). | ||
== Structure == | == Structure == | ||
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:N-C Full ALK Structure.PNG|600 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" /> | 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:N-C Full ALK Structure.PNG|600 px|right|thumb|Figure 1. Overview of Anaplastic Lymphoma Kinase Structure with domains where known structure are color coordinated and other domains are grayed out.]] 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" /> | ||
=== Domains === | === Domains === | ||
==== Three Helix Bundle-like Domain ==== | ==== Three Helix Bundle-like Domain ==== | ||