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Sci. Signal., 14 September 2010
Vol. 3, Issue 139, p. re6
[DOI: 10.1126/scisignal.3139re6]


ABL Tyrosine Kinases: Evolution of Function, Regulation, and Specificity

John Colicelli*

Department of Biological Chemistry, Molecular Biology Institute and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

Gloss: ABL-family proteins couple a highly regulated tyrosine kinase domain with an actin-binding and -bundling domain to carry out a set of unique and essential functions. The ABL genes are among the earliest identifiable genes encoding tyrosine kinases, and they show remarkable sequence conservation. Gene duplication produced two vertebrate ABL paralogs with specialized properties. ABL1 evolved nuclear localization signals and a DNA binding domain to mediate damage repair functions. ABL2 developed additional binding domains for actin and microtubules, extending its cytoskeletal remodeling functions. This Review surveys the recent literature and available databases with a focus on ABL evolution and the mechanisms regulating ABL's catalytic activity and substrate specificity. This Review contains 7 figures, 2 tables, and 248 references. A better understanding of these properties could facilitate the design of new treatments for malignancies driven by ABL fusion proteins.

* Corresponding author. Telephone, 310-825-1251; fax, 310-206-1929; e-mail, colicelli{at}

Citation: J. Colicelli, ABL Tyrosine Kinases: Evolution of Function, Regulation, and Specificity. Sci. Signal. 3, re6 (2010).

The Capable ABL: What Is Its Biological Function?.
J. Y. J. Wang (2014)
Mol. Cell. Biol. 34, 1188-1197
   Abstract »    Full Text »    PDF »
Protein kinase G increases antioxidant function in lung microvascular endothelial cells by inhibiting the c-Abl tyrosine kinase.
R. S. Stephens, L. E. Servinsky, O. Rentsendorj, T. M. Kolb, A. Pfeifer, and D. B. Pearse (2014)
Am J Physiol Cell Physiol 306, C559-C569
   Abstract »    Full Text »    PDF »
c-Abl phosphorylates {alpha}-synuclein and regulates its degradation: implication for {alpha}-synuclein clearance and contribution to the pathogenesis of Parkinson's disease.
A.-L. Mahul-Mellier, B. Fauvet, A. Gysbers, I. Dikiy, A. Oueslati, S. Georgeon, A. J. Lamontanara, A. Bisquertt, D. Eliezer, E. Masliah, et al. (2014)
Hum. Mol. Genet.
   Abstract »    Full Text »    PDF »
Two-state dynamics of the SH3-SH2 tandem of Abl kinase and the allosteric role of the N-cap.
C. Corbi-Verge, F. Marinelli, A. Zafra-Ruano, J. Ruiz-Sanz, I. Luque, and J. D. Faraldo-Gomez (2013)
PNAS 110, E3372-E3380
   Abstract »    Full Text »    PDF »
Systematic identification of Class I HDAC substrates.
T. Li, B. Song, Z. Wu, M. Lu, and W.-G. Zhu (2013)
Brief Bioinform
   Abstract »    Full Text »    PDF »
c-Abl-dependent Molecular Circuitry Involving Smad5 and Phosphatidylinositol 3-Kinase Regulates Bone Morphogenetic Protein-2-induced Osteogenesis.
N. Ghosh-Choudhury, C. C. Mandal, F. Das, S. Ganapathy, S. Ahuja, and G. Ghosh Choudhury (2013)
J. Biol. Chem. 288, 24503-24517
   Abstract »    Full Text »    PDF »
Non-receptor-tyrosine Kinases Integrate Fast Glucocorticoid Signaling in Hippocampal Neurons.
S. Yang, F. Roselli, A. V. Patchev, S. Yu, and O. F. X. Almeida (2013)
J. Biol. Chem. 288, 23725-23739
   Abstract »    Full Text »    PDF »
Abelson Interactor 1 (Abi1) and Its Interaction with Wiskott-Aldrich Syndrome Protein (Wasp) Are Critical for Proper Eye Formation in Xenopus Embryos.
A. Singh, E. F. Winterbottom, Y. J. Ji, Y.-S. Hwang, and I. O. Daar (2013)
J. Biol. Chem. 288, 14135-14146
   Abstract »    Full Text »    PDF »
Phosphotyrosine Signaling Proteins that Drive Oncogenesis Tend to be Highly Interconnected.
G. Koytiger, A. Kaushansky, A. Gordus, J. Rush, P. K. Sorger, and G. MacBeath (2013)
Mol. Cell. Proteomics 12, 1204-1213
   Abstract »    Full Text »    PDF »
Structure and Dynamic Regulation of Abl Kinases.
S. Panjarian, R. E. Iacob, S. Chen, J. R. Engen, and T. E. Smithgall (2013)
J. Biol. Chem. 288, 5443-5450
   Abstract »    Full Text »    PDF »
RIN1 orchestrates the activation of RAB5 GTPases and ABL tyrosine kinases to determine the fate of EGFR.
K. Balaji, C. Mooser, C. M. Janson, J. M. Bliss, H. Hojjat, and J. Colicelli (2012)
J. Cell Sci. 125, 5887-5896
   Abstract »    Full Text »    PDF »
H. Kalwa, J. L. Sartoretto, S. M. Sartoretto, and T. Michel (2012)
J. Biol. Chem. 287, 29147-29158
   Abstract »    Full Text »    PDF »
Abl Family Kinases Modulate T Cell-Mediated Inflammation and Chemokine-Induced Migration Through the Adaptor HEF1 and the GTPase Rap1.
J. J. Gu, C. P. Lavau, E. Pugacheva, E. J. Soderblom, M. A. Moseley, and A. M. Pendergast (2012)
Science Signaling 5, ra51
   Abstract »    Full Text »    PDF »
Caveolar domain organization and trafficking is regulated by Abl kinases and mDia1.
A. Echarri, O. Muriel, D. M. Pavon, H. Azegrouz, F. Escolar, M. C. Terron, F. Sanchez-Cabo, F. Martinez, M. C. Montoya, O. Llorca, et al. (2012)
J. Cell Sci. 125, 3097-3113
   Abstract »    Full Text »    PDF »
Activation of Abl Family Kinases in Solid Tumors.
S. S. Ganguly and R. Plattner (2012)
Genes & Cancer 3, 414-425
   Abstract »    Full Text »    PDF »
Proteome-wide Detection of Abl1 SH3-binding Peptides by Integrating Computational Prediction and Peptide Microarray.
Z. Xu, T. Hou, N. Li, Y. Xu, and W. Wang (2012)
Mol. Cell. Proteomics 11, O111.010389
   Abstract »    Full Text »    PDF »
Characterization of the Src/Abl Hybrid Kinase SmTK6 of Schistosoma mansoni.
S. Beckmann, S. Hahnel, K. Cailliau, M. Vanderstraete, E. Browaeys, C. Dissous, and C. G. Grevelding (2011)
J. Biol. Chem. 286, 42325-42336
   Abstract »    Full Text »    PDF »
The SH2 Domain-Containing Proteins in 21 Species Establish the Provenance and Scope of Phosphotyrosine Signaling in Eukaryotes.
B. A. Liu, E. Shah, K. Jablonowski, A. Stergachis, B. Engelmann, and P. D. Nash (2011)
Science Signaling 4, ra83
   Abstract »    Full Text »    PDF »

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