Sandbox Reserved 1705: Difference between revisions
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== Introduction == | == Introduction == | ||
[[Image: | [[Image:ALK_Domains.png|350 px|right|thumb|Figure 1. Outline of the domains and regions of anaplastic lymphoma kinase]] | ||
Anaplastic lymphoma kinase is a [https://en.wikipedia.org/wiki/Receptor_tyrosine_kinase receptor tyrosine kinase] (RTK) important to the regulation of functions within the central nervous system <ref name="Reshetnyak">PMID:34819673</ref>. RTKs are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. ALK activates pathways that promote cell growth and proliferation, similar to the [[Insulin Receptor|Insulin Receptor (IR)]]. These pathways include, but are not limited to, the [https://en.wikipedia.org/wiki/MAPK/ERK_pathway ERK], [https://en.wikipedia.org/wiki/JAK-STAT_signaling_pathway JAK], and [https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway PI3K] pathways. ALK is composed of two identical monomers consisting of seven unique domains and two intermixed regions. Among these, probably the most notable is the glycine-rich region (GlyR), characterized by helical structures formed by glycine residues. Other domains are archetypal of RTK activation and regulation. The preferred ligand for binding is AUG which binds in a dimeric fashion to ALK. When the ligand has bound, there is a conformational change that is covered in more detail in Figure 2 and it's accompanying text. In order to determine the atomic details of human ALK dimerization and activation by AUG, the methods of [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryo-electron microscopy],[https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance_spectroscopy nuclear magnetic resonance], and [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray crystallography] were utilized <ref name="Reshetnyak">PMID:34819673</ref> . Anaplastic lymphoma kinase is a proto-oncogene with mutations associated with various types of cancers, including non-small-cell lung cancer, anaplastic large cell lymphoma, squamous cell carcinoma, and inflammatory myofibroblastic cancer <ref name="Palmer">PMID:19459784</ref>. ALK is a referred to as a proto-oncogene because certain mutations in it's protein sequence are known to have a strong positive association with the development of cancerous cells. | Anaplastic lymphoma kinase is a [https://en.wikipedia.org/wiki/Receptor_tyrosine_kinase receptor tyrosine kinase] (RTK) important to the regulation of functions within the central nervous system <ref name="Reshetnyak">PMID:34819673</ref>. RTKs are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. ALK activates pathways that promote cell growth and proliferation, similar to the [[Insulin Receptor|Insulin Receptor (IR)]]. These pathways include, but are not limited to, the [https://en.wikipedia.org/wiki/MAPK/ERK_pathway ERK], [https://en.wikipedia.org/wiki/JAK-STAT_signaling_pathway JAK], and [https://en.wikipedia.org/wiki/PI3K/AKT/mTOR_pathway PI3K] pathways. ALK is composed of two identical monomers consisting of seven unique domains and two intermixed regions. Among these, probably the most notable is the glycine-rich region (GlyR), characterized by helical structures formed by glycine residues. Other domains are archetypal of RTK activation and regulation. The preferred ligand for binding is AUG which binds in a dimeric fashion to ALK. When the ligand has bound, there is a conformational change that is covered in more detail in Figure 2 and it's accompanying text. In order to determine the atomic details of human ALK dimerization and activation by AUG, the methods of [https://en.wikipedia.org/wiki/Cryogenic_electron_microscopy cryo-electron microscopy],[https://en.wikipedia.org/wiki/Nuclear_magnetic_resonance_spectroscopy nuclear magnetic resonance], and [https://en.wikipedia.org/wiki/X-ray_crystallography X-ray crystallography] were utilized <ref name="Reshetnyak">PMID:34819673</ref> . Anaplastic lymphoma kinase is a proto-oncogene with mutations associated with various types of cancers, including non-small-cell lung cancer, anaplastic large cell lymphoma, squamous cell carcinoma, and inflammatory myofibroblastic cancer <ref name="Palmer">PMID:19459784</ref>. ALK is a referred to as a proto-oncogene because certain mutations in it's protein sequence are known to have a strong positive association with the development of cancerous cells. | ||
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==== Tyrosine Phosphorylation Mechanism ==== | ==== Tyrosine Phosphorylation Mechanism ==== | ||
[[Image: | [[Image:ALK_Tyrosine_Phosphorylation.png|350 px|left|thumb|Figure 4. Tyrosine phosphorylation mechanism]] | ||
