SandboxPKA: Difference between revisions
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{{STRUCTURE_1opl| PDB=1opl | SIZE=400 | SCENE= |right| CAPTION=ABL1 homo-dimer complex with two ligands}} | {{STRUCTURE_1opl| PDB=1opl | SIZE=400 | SCENE= |right| CAPTION=ABL1 homo-dimer complex with two ligands}} | ||
The '''c-Abl protein 1 (ABL1)''', also known as '''Abelson kinase''', is a [http://www.proteopedia.org/wiki/index.php/Proto-oncogene_tyrosine-protein_kinase non-receptor tyrosine kinase] that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. <ref>PMID:9037071</ref> <ref>PMID:11114745</ref> Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. In more than 90% cases, chronic | The '''c-Abl protein 1 (ABL1)''', also known as '''Abelson kinase''', is a [http://www.proteopedia.org/wiki/index.php/Proto-oncogene_tyrosine-protein_kinase non-receptor tyrosine kinase] that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. <ref>PMID:9037071</ref> <ref>PMID:11114745</ref> Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. In more than 90% cases, chronic myeloid leukemia (CML) is caused by a chromosomal abnormality that results in the formation of the Philadelphia chromosome. This chromosome is formed by fusion between Abelson (Abl) tyrosine kinase gene at chromosome 9 and break point cluster region (BCR) gene at chromosome 22, resulting in the chimeric oncogene BCR-Abl and a constitutively active BCR-Abl tyrosine kinase. The Bcr-Abl pathway has many downstream pathways including the Ras/MAPK pathway, which leads to increased proliferation due to increased growth factor-independent cell growth. It also affects the Src/Pax/Fak/Rac pathway. This affects the cytoskeleton, which leads to increased cell motility and decreased adhesion. The PI/PI3K/AKT/BCL-2 pathway is also affected. The last pathway that Bcr-Abl affects is the JAK/STAT pathway, which is responsible for proliferation. | ||
Small molecule inhibitors of BCR-Abl that bind to the kinase domain can be used to treat CML <ref>PMID:12154025</ref> | Small molecule inhibitors of BCR-Abl that bind to the kinase domain can be used to treat CML <ref>PMID:12154025</ref> | ||
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=='''Authors'''== | =='''Authors'''== | ||
Almudena Chaves Pérez; Julio César Corral Serrano; Cristina Murga Montesinos. | Some morphs and scenes were reproduced from the pages from David Canner. Almudena Chaves Pérez; Julio César Corral Serrano; Cristina Murga Montesinos. | ||
=='''References'''== | =='''References'''== | ||
{{Reflist}} | {{Reflist}} | ||
