High impact information on Abl1

• We identified WAVE-1 in a screen for rat brain A kinase-anchoring proteins (AKAPs), which bind to the SH3 domain of the Abelson tyrosine kinase (Abl) [1].
• At least two of the ArgBP2/nArgBP2 binding partners, synaptojanin 2B and WAVE2, undergo ubiquitination and Abl-dependent tyrosine phosphorylation [2].
• The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple regulatory mechanisms converging on the actin cytoskeleton [2].
• Tyr-161 shares similarity to the consensus sequence for phosphorylation by the nonreceptor tyrosine kinases Abl and Arg [3].
• Moreover, treatment of neurons with two structurally distinct and highly selective Abl inhibitors, PD173955 and Gleevec, blocks HK-induced phosphorylation of IkappaB-beta at Tyr-161 and induces neuronal apoptosis [3].

Biological context of Abl1

• Tyrosine-phosphorylated p62(dok) from cells expressing p210(bcr-abl) bound directly to the SH2 domains of Abl and CrkL in a gel overlay assay [4].
• Our data provide insight into the role of highly conserved residues in the Crk-SH3-C, suggesting a mechanism for how the linker and the Crk-SH3-C function in the transactivation of the Abl tyrosine kinase [5].
• Using a developing hippocampal culture as a model, we found that the inhibition of Abl kinases by STI571 leads to a remarkable simplification of dendritic branching similar to the phenotype caused by an increased activity of small GTPase RhoA [6].
• Although Abl family kinases also are localized in dendrites and are implicated in postsynaptic functions, it is not clear how Abl kinases regulate dendritic morphogenesis [6].

Anatomical context of Abl1

• Non-receptor tyrosine kinase Abl is a well known regulator of the actin-cytoskeleton, including the formation of stress fibers and membrane ruffles [7].
• In contrast, neurons expressing a constitutively active v-abl construct (CA-Abl) show an exuberant microtubule-associated protein 2-positive (MAP2-positive) dendrite outgrowth, suggesting that Abl modulates dendritic growth [6].

Associations of Abl1 with chemical compounds

• The mutant protein AS2 is active as a tyrosine kinase and can phosphorylate Abl substrates, such as the C-terminal repeated domain of RNA polymerase II [8].
• These results have implications for the use of PP1 in investigating intracellular signaling and suggest that PP1 or related compounds may be useful in the treatment of malignant diseases associated with dysregulated c-Kit or Abl tyrosine kinase activity [9].
• However, the effects of both NPY and VEGF on the permeability of the RAEC monolayer were blocked with equal concentration dependence by STI571 (imatinib mesylate), which is an inhibitor of Abl tyrosine kinase in the nucleus and/or cytoplasm [10].

References