4xli

Structural highlights

Function

ABL2_MOUSE Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in 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 MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL or DOK1. Required for adhesion-dependent phosphorylation of ARHGAP35 which promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1 (PubMed:22810897).^{[1] [2] [3] [4] [5] [6] [7] [8]}

See Also

• Tyrosine kinase 3D structures

References

1. ↑ Kain KH, Klemke RL. Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes. J Biol Chem. 2001 May 11;276(19):16185-92. Epub 2001 Jan 19. PMID:11279004 doi:10.1074/jbc.M100095200
2. ↑ Wang Y, Miller AL, Mooseker MS, Koleske AJ. The Abl-related gene (Arg) nonreceptor tyrosine kinase uses two F-actin-binding domains to bundle F-actin. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14865-70. PMID:11752434 doi:10.1073/pnas.251249298
3. ↑ Tanis KQ, Veach D, Duewel HS, Bornmann WG, Koleske AJ. Two distinct phosphorylation pathways have additive effects on Abl family kinase activation. Mol Cell Biol. 2003 Jun;23(11):3884-96. PMID:12748290
4. ↑ Plattner R, Koleske AJ, Kazlauskas A, Pendergast AM. Bidirectional signaling links the Abelson kinases to the platelet-derived growth factor receptor. Mol Cell Biol. 2004 Mar;24(6):2573-83. PMID:14993293
5. ↑ Bradley WD, Hernández SE, Settleman J, Koleske AJ. Integrin signaling through Arg activates p190RhoGAP by promoting its binding to p120RasGAP and recruitment to the membrane. Mol Biol Cell. 2006 Nov;17(11):4827-36. PMID:16971514 doi:10.1091/mbc.e06-02-0132
6. ↑ Boyle SN, Koleske AJ. Use of a chemical genetic technique to identify myosin IIb as a substrate of the Abl-related gene (Arg) tyrosine kinase. Biochemistry. 2007 Oct 16;46(41):11614-20. PMID:17892306 doi:10.1021/bi701119s
7. ↑ Gu JJ, Lavau CP, Pugacheva E, Soderblom EJ, Moseley MA, Pendergast AM. Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1. Sci Signal. 2012 Jul 17;5(233):ra51. PMID:22810897 doi:10.1126/scisignal.2002632
8. ↑ Koleske AJ, Gifford AM, Scott ML, Nee M, Bronson RT, Miczek KA, Baltimore D. Essential roles for the Abl and Arg tyrosine kinases in neurulation. Neuron. 1998 Dec;21(6):1259-72. PMID:9883720 doi:10.1016/s0896-6273(00)80646-7
9. ↑ Ha BH, Simpson MA, Koleske AJ, Boggon TJ. Structure of the ABL2/ARG kinase in complex with dasatinib. Acta Crystallogr F Struct Biol Commun. 2015 Apr;71(Pt 4):443-8. doi:, 10.1107/S2053230X15004793. Epub 2015 Mar 20. PMID:25849507 doi:http://dx.doi.org/10.1107/S2053230X15004793