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Search results 1 to 4 out of 4 for Abl1

Category restricted to ProteinDomain (x)

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Category: ProteinDomain
Type Details Score
Protein Domain
Type: Family
Description: This entry includes animal ABL1 and viral oncogene products that are homologous to ABL1 []. ABL1 plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodelling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis [, , , ]. Normal ABL1 can serve as a tumour suppressor and therapeutic target in leukemias expressing oncogenic forms of the kinase [].ABL tyrosine kinases are nonreceptor tyrosine kinases containing an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity. This cassette is coupled to an actin-binding and -bundling domain, which makes ABL proteins capable of connecting phosphoregulation with actin-filament reorganization. Two vertebrate ABL tyrosine kinases have been identified, ABL1 and ABL2 [].A downstream effector of RAS, RIN1, have been found to bind to the SH3 and SH2 domains of ABL1/ABL2 to relieve autoinhibition and regulate their activity [].
Protein Domain
Type: Family
Description: This group represents protein CABLES (CDK5 and ABL1 enzyme substrate), including CABLES1 and CABLES2 [, ]. CABLES1 is a cyclin-dependent kinase binding protein, primarily involved in cell cycle regulation []. CABLES1 binds to different functional domains of p53 and p73 and modifies their cell death-inducing activities []. It may be a tumour suppressor in human ovarian cancer []. CABLES2 is involved in both p53-mediated and p53-independent apoptotic pathways [].
Protein Domain
Type: Domain
Description: The F-actin binding domain forms a compact bundle of four antiparallel α-helices, which are arranged in a left-handed topology. Binding of F-actin to the F-actin binding domain may result in cytoplasmic retention and subcellular distribution of the protein, as well as possible inhibition of protein function []. Proteins containing this domain include tyrosine-protein kinases Abl1, which is a 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 [, ]. Abl1 is linked to different forms of leukemia in humans.
Protein Domain
Type: Domain
Description: ABL-family proteins are highly conserved tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. Several types of posttranslational modifications control ABL catalytic activity, subcellular localization, and stability, with consequences for both cytoplasmic and nuclear ABL functions. Binding partners provide additional regulation of ABL catalytic activity, substrate specificity, and downstream signaling. By combining this cassette with actin-binding and -bundling domains, ABL proteins are capable of connecting phosphoregulation with actin-filament reorganization []. Vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ABL1 includes nuclear localization signals and a DNA binding domain which is used to mediate DNA damage-repair functions, while ABL2 has additional binding capacity for actin and for microtubules to enhance its cytoskeletal remodeling functions. SH2 is involved in several autoinhibitory mechanism that constrain the enzymatic activity of the ABL-family kinases. In one mechanism SH2 and SH3 cradle the kinase domain while a cap sequence stabilizes the inactive conformation resulting in a locked inactive state. Another involves phosphatidylinositol 4,5-bisphosphate (PIP2) which binds the SH2 domain through residues normally required for phosphotyrosine binding in the linker segment between the SH2 and kinase domains. The SH2 domain contributes to ABL catalytic activity and target site specificity. It is thought that the ABL catalytic site and SH2 pocket have co-evolved to recognize the same sequences. Recent work now supports a hierarchical processivity model in which the substrate target site most compatible with ABL kinase domain preferences is phosphorylated with greatest efficiency. If this site is compatible with the ABL SH2 domain specificity, it will then reposition and dock in the SH2 pocket. This mechanism also explains how ABL kinases phosphorylates poor targets on the same substrate if they are properly positioned and how relatively poor substrate proteins might be recruited to ABL through a complex with strong substrates that can also dock with the SH2 pocket [].This entry includes the SH2 domain of ABL-family proteins. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites [, , , ].