Sandbox Reserved 1713: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
The anaplastic lymphoma kinase was first discovered in 1994 as a tyrosine kinase in a type of lymphoma cancer cell. ALK is a specific type of [https://link.springer.com/article/10.1186/s12943-018-0782-4 RTK] which plays a huge role in transmembrane signaling and communication within the cell. ALK is commonly expressed in the development of the nervous system. Anaplastic Lymphoma Kinase receptor is a membrane-bound tyrosine [https://pubmed.ncbi.nlm.nih.gov/32114309/ kinase]. The ALK transfers a phosphate group from [https://www.ncbi.nlm.nih.gov/books/NBK553175/ ATP] to a tyrosine residue on an enzyme which activates a signaling cascade, and ALK becomes activated when a ligand called [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789956/ ALKAL] binds to the binding surface on an extracellular domain of ALK. ALK is an integral membrane protein. Abnormal forms of ALK are closely related to the formation of several cancers. | The anaplastic lymphoma kinase was first discovered in 1994 as a tyrosine kinase in a type of lymphoma cancer cell. ALK is a specific type of [https://link.springer.com/article/10.1186/s12943-018-0782-4 RTK] which plays a huge role in transmembrane signaling and communication within the cell. ALK is commonly expressed in the development of the nervous system. Anaplastic Lymphoma Kinase receptor is a membrane-bound tyrosine [https://pubmed.ncbi.nlm.nih.gov/32114309/ kinase]. The ALK transfers a phosphate group from [https://www.ncbi.nlm.nih.gov/books/NBK553175/ ATP] to a tyrosine residue on an enzyme which activates a signaling cascade, and ALK becomes activated when a ligand called [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789956/ ALKAL] binds to the binding surface on an extracellular domain of ALK. ALK is an integral membrane protein. Abnormal forms of ALK are closely related to the formation of several cancers. | ||
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | ||
== Structure & Function == | == Structure & Function == | ||
The active state of the kinase is when two monomers have completed a conformational change and moved across the membrane to form a <scene name='90/904317/Dimer_full_colored/3'>dimer</scene>. | The active state of the kinase is when two monomers have completed a conformational change and moved across the membrane to form a <scene name='90/904317/Dimer_full_colored/3'>dimer</scene>. | ||
| Line 19: | Line 18: | ||
<scene name='90/904318/Alkal1membraneinteraction/2'>ALKAL's residues that interact with membrane</scene> | <scene name='90/904318/Alkal1membraneinteraction/2'>ALKAL's residues that interact with membrane</scene> | ||
===Conformational Change=== | ===Conformational Change=== | ||
The anaplastic lymphoma kinase activating ligand (ALKAL) binds to the <scene name='90/904318/Alk-alkal_binding_surface/2'>binding surface</scene> on the ALK at the TNFL domain. This induces a conformational change which allows for the PXL and the GlyR domains to hinge forward.<ref>DOI: 10.1038/s41586-021-04140-8</ref> (Figure 2) ALKAL-bound ALK is now ready to dimerize with another ALK-ALKAL complex | |||
===Movement across the membrane=== | ===Movement across the membrane=== | ||
The negatively charged phosphate groups on the cell membrane interact with the highly conserved positively charged residues on ALKAL ligand that face the membrane, which stabilizes the ligand to bind to ALK even better. <ref>DOI: 10.1038/s41586-021-04140-8</ref> | The negatively charged phosphate groups on the cell membrane interact with the highly conserved positively charged residues on ALKAL ligand that face the membrane, which stabilizes the ligand to bind to ALK even better. <ref>DOI: 10.1038/s41586-021-04140-8</ref> | ||