1ju5: Difference between revisions
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{{STRUCTURE_1ju5| PDB=1ju5 | SCENE= }} | {{STRUCTURE_1ju5| PDB=1ju5 | SCENE= }} | ||
===Ternary complex of an Crk SH2 domain, Crk-derived phophopeptide, and Abl SH3 domain by NMR spectroscopy=== | |||
{{ABSTRACT_PUBMED_12384576}} | |||
=== | ==Disease== | ||
[[http://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Note=A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). | |||
==Function== | |||
[[http://www.uniprot.org/uniprot/CRK_HUMAN CRK_HUMAN]] The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling.<ref>PMID:1630456</ref><ref>PMID:11870224</ref><ref>PMID:17515907</ref> [[http://www.uniprot.org/uniprot/ABL1_HUMAN ABL1_HUMAN]] Non-receptor tyrosine-protein 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. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-153' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. ABL1 acts also as a regulator of multiple pathological signaling cascades during infection. Several known tyrosine-phosphorylated microbial proteins have been identified as ABL1 substrates. This is the case of A36R of Vaccinia virus, Tir (translocated intimin receptor) of pathogenic E.coli and possibly Citrobacter, CagA (cytotoxin-associated gene A) of H.pylori, or AnkA (ankyrin repeat-containing protein A) of A.phagocytophilum. Pathogens can highjack ABL1 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.<ref>PMID:9037071</ref><ref>PMID:9144171</ref><ref>PMID:9461559</ref><ref>PMID:10391250</ref><ref>PMID:12379650</ref><ref>PMID:11971963</ref><ref>PMID:12531427</ref><ref>PMID:12672821</ref><ref>PMID:15556646</ref><ref>PMID:15031292</ref><ref>PMID:15886098</ref><ref>PMID:15657060</ref><ref>PMID:16943190</ref><ref>PMID:16678104</ref><ref>PMID:17306540</ref><ref>PMID:17623672</ref><ref>PMID:18328268</ref><ref>PMID:18945674</ref><ref>PMID:19891780</ref><ref>PMID:20417104</ref><ref>PMID:16424036</ref><ref>PMID:20357770</ref> [[http://www.uniprot.org/uniprot/CRK_MOUSE CRK_MOUSE]] The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling. | |||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
<ref group="xtra">PMID:012384576</ref><references group="xtra"/> | <ref group="xtra">PMID:012384576</ref><references group="xtra"/><references/> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||