Biochemistry; Biophysics; Molecular Biology; Morphogenesis; Schizophrenia; Stress, Physiological
Research SummaryOur lab has a long-standing interest in understanding how growth factor and adhesion receptor signaling controls changes in cell shape and movement. We have pursued these studies primarily in three model systems: fibroblast migration, breast cancer cell invasion and metastasis, and the formation and stabilization of neuronal dendrites and dendritic spines.In each of these systems, we have developed biochemical approaches to elucidate signaling mechanisms, genetic approaches in mice to manipulate these signaling mechanisms, and a complementary collection of quantitative assays of cell migration, in vivo metastasis, electrophysiology, neuroanatomy, and animal behavior as functional readouts.
Extensive Research Description
Identification and characterization of Mediator-containing RNA polymerase II holoenzyme. As an undergraduate student with Henry Pitot at the University of Wisconsin, I helped characterize the gene encoding the barbiturate-induced aldehyde dehydrogenase from rat liver. This project exposed me to the compelling idea that an environmental cue, in this case phenobarbital, can dramatically change the gene-expression profile of the hepatocyte. My Ph.D. thesis research with Rick Young at the Whitehead Institute/MIT pursued my growing fascination with the complicated process of how genes get turned on. I identified an “initiation factor” required for RNA polymerase II to begin transcription of protein-coding genes in yeast. I demonstrated that this factor was part of a large complex, which we called the SRB complex (for suppressor of RNA polymerase B/II), contemporaneously discovered and named Mediator by Roger Kornberg’s lab. I went on to purify RNA polymerase II in complex with SRB complex/Mediator and a large subset of the general transcription factors. I demonstrated that this RNA polymerase II “holoenzyme” (a term I coined) appears to be the form most readily recruited to promoters in vivo and was responsive to transcriptional activators, a feature not observed with purified RNA pol II and general transcription factors alone. Together, my experiments revised models for how RNA polymerase II assembles onto gene sequences and how transcriptional activator proteins stimulate this process.
a. Dunn, T.J., Koleske, A.J., Lindahl, R., and Pitot, H.C. (1989) Phenobarbital-inducible aldehyde dehydrogenase in the rat. cDNA sequence and regulation of the mRNA by phenobarbital in responsive rats. J. Biol. Chem. 264:13057-13065.
b. Koleske, A.J., Buratowski, S., Nonet, M., and Young, R.A. (1992) A novel transcription factor reveals a functional link between the RNA polymerase II CTD and TFIID. Cell 69: 883-894.
c. Thompson, C.M., Koleske, A.J., Chao, D.M. and Young, R.A. (1993) A multisubunit complex associated with the RNA polymerase II CTD and TATA-binding protein in yeast.Cell 73: 1361-1375.
d. Koleske, A.J., and Young, R.A. (1994) An RNA polymerase II holoenzyme responsive to activators. Nature 368: 466-469. This letter was featured in News and Views: Carey, M. (2004) Simplifying the complex. Nature 368: 402-403.
Abl family kinases regulate cell shape and movement. The Abl (Abl1) nonreceptor tyrosine kinase was originally identified in the 1970s as a proto-oncogene associated with mouse and human leukemias, but the normal physiological function of the Abl family kinases was unknown. In work I began as a postdoc with David Baltimore at MIT that continues in my own lab, I used genetic and cell biological approaches to demonstrate that the Abl1/Abl and Abl2/Arg kinases play diverse roles as key regulators of cell morphogenesis and migration in tissues and cell types.In one early study we demonstrated that ablation of Abl1 and Abl2 in mice disrupts neuroepithelial cell morphogenesis, leading to defects in neurulation. Subsequent work from our lab demonstrated key requirements for these kinases in neuronal morphogenesis, neuronal dendrite stability, fibroblast migration, breast cancer cell invasion and metastasis, and macrophage engulfment of parasites. Our studies at the cellular level have identified key roles for Abl1 and Abl2 as mediators between cell surface adhesion and growth factor receptors and the coordination of adhesion dynamics and actin cytoskeletal rearrangements.
a. *Koleske, A.J., Gifford, A. M., Scott, M. L., Nee, M., Bronson, R. T., Miczek, K., and Baltimore, D. (1998) Essential roles for the Abl and Arg tyrosine kinases in neurulation. Neuron 21: 1259-1272. *Corresponding author
b. Miller, A.L., Wang, Y., Mooseker, M., and Koleske, A.J. (2004) The Abl-related gene (Arg) requires its F-actin:microtubule crosslinking activity to regulate lamellipodial dynamics during fibroblast adhesion. J. Cell Biol., 165: 407-419.
This was a featured article in JCB: Wells, W.A. (2004) Arg links actin and microtubules.J. Cell Biol. 165: 294-295
c. Lapetina, S., Mader, C.C., Machida, K., Mayer, B.J., and Koleske, A.J.(2009) Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion. J. Cell Biol., 185: 503-19
This article was featured in the Nature Publishing Group’s Cell Migration Gateway.K. Bauman “Interactions at the front: Arg(uing) with cortactin”
d. Gil-Henn, H., Patsialou, A., Condeelis, J., and Koleske, A.J. (2013) Arg promotes invasion and attenuates proliferation of breast cancer in vivo. Oncogene, 32(21):2622-30.PMCID:PMC3473103
Regulation of Abl family kinase activity in normal cells and invasive breast cancer cells. One major focus of our work has been to understand how Abl and Arg translate signals from cell surface receptors into intracellular signaling pathways. In early work, we established a biochemical system using purified recombinant Abl family kinases to elucidate activation mechanisms.Our work showed that two conserved phosphorylation events mediate >10-fold activation of Abl and Arg kinase activities. Phosphorylation of a tyrosine in the SH2 domain kinase linker is mediated by autophosphorylation of the kinase in trans, while phosphorylation on the activation loop is mediated by Src family kinases. We also discovered that integrin adhesion receptors and growth factor receptors are potent activators of Abl family kinases in diverse cell types. We found that epidermal growth factor signaling through Src mediates Arg kinase activation in breast cancer cells, and this is a key trigger for invadopodium formation and invasive migration. We found that the Arg interacts with integrin beta 1 subunit tail via a series of discrete binding and phosphorylation events and we have mapped key interaction interfaces that are critical for these interactions. Our ongoing work is using structural approaches to understand the integrin:Abl2 activation mechanisms at atomic level resolution. We are also developing single molecule imaging approaches in cells to understand how growth factor and adhesion receptor engagement affects recruitment of Arg to the cell membrane and how these events relate spatiotemporally to changes in cytoskeletal structure and cell movement.
a. Tanis, K., Duewel, H.S., Veach, D., Bornmann, W. and Koleske, A.J. (2003) Two distinct phosphorylation pathways have additive effects on Abl family kinase activation. Mol. Cell. Biol. 23: 3884-3896.
b. Warren, M.S., Gourley, S.L., Lin, Y.-C., Simpson, M.A., Taylor, J.R., Greer, C.A. and Koleske, A.J. (2012) Integrin β1 signals through Arg to regulate postnatal dendritic arborization, synapse density, and behavior. J Neurosci. 32(8):2824-34. PMCID:PMC3313657
c. Mader, C.C., Oser, M., Magalhaes, M., *Condeelis, J., *Koleske, A.J., and Gil-Henn, H. (2011) EGF signaling through a Src-Arg-cortactin relay regulates breast cancer invasiveness by controlling invadopodia maturation and function. Cancer Research, 71(5):1730-41. PMCID:PMC3057139
*Corresponding authors – Hava Gil-Henn was an Associate Research Scientist in the Koleske lab at time of publication
d. Simpson, M.A., Bradley, W.D., Harburger, D., Parsons, M., Calderwood, D.A., and Koleske, A.J. (2015) Direct interactions with the integrin beta1 cytoplasmic tail modulate Abl2/Arg kinase activity. J Biol Chem, 290(13):8360-72. PMCID: PMC4375489
4. Regulation of dendrite, dendritic spine, and synapse development and stability. Building on our findings that Abl family kinases are key regulators of neuronal development and function, we have elucidated key biochemical pathways that control long-term dendrite and dendritic spine stability. In addition to our identification of upstream activators (see #3 above), this work has led us to identify the Rho inhibitor p190RhoGAP and actin polymerization and stability regulator cortactin as key interaction partners and substrates of Abl family kinases. Our work has revealed that many components of these pathways (integrins a3 and b1, Arg, p190RhoGAP, p120RasGAP, Rho, cortactin) are essential for long-term maintenance of normal synapse and dendrite structure. For example, although neurons develop normally in mice lacking integrin a3, b1, or Arg through postnatal day 21, they subsequently begin to lose synapses and dendrites, leading to significant synapse loss and dendritic regression by early adulthood. This neuronal destabilization is accompanied by significant deficits in behaviors that require proper hippocampal and prefrontal cortical function. Importantly, mutations or microdeletions affecting several of the proteins we have implicated in dendrite, spine, and synapse development and stability (integrins a3 and b1, Arg, p190RhoGAP, SHP-2, GluN2B) are associated with neurological and psychiatric disorders in humans underscoring the importance of our work for understanding human brain function. Because this work has highlighted the fundamental instructive role of extracellular matrix (ECM) in dendrite development, a major current focus is to identify key ECM molecules that regulate dendrite development and elucidating their mechanisms of action. We are also interested understanding how pathological states (e.g. chronic stress) impact these signaling mechanisms to trigger dendrite, dendritic spine, and synapse loss.
a. Moresco, E. M. Y., Donaldson, S., Williamson, A., and Koleske, A.J. (2005) Integrin-mediated dendrite branch maintenance requires Abelson (Abl) family kinases. J Neurosci., 25: 6105-6118
This was a featured article in J Neuroscience: (2005) EnAbling dendrite branching. J Neurosci 25: 26.
b. Gourley, S.L., Olevska, A., Warren, M.S., Taylor, J., and Koleske, A.J. (2012) Arg kinase regulates prefrontal dendritic spine refinement and cocaine-induced plasticity. J Neurosci. 32(7):2314-23. PMCID:PMC3386297.
c. Warren, M.S., Gourley, S.L., Lin, Y.-C., Simpson, M.A., Taylor, J.R., Greer, C.A. and Koleske, A.J. (2012) Integrin β1 signals through Arg to regulate postnatal dendritic arborization, synapse density, and behavior. J Neurosci. 32(8):2824-34. PMCID:PMC3313657
d. Kerrisk, M.E., Greer, C.A., and Koleske, A.J. (2013) Integrin α3 is required for late postnatal stability of dendritic spines, synapses, dendritic arbor complexity, and mouse behavior. J Neurosci. 33(16):6742-52. PMCID:PMC3711182
Mentoring, Education, and Science Policy. I am very strongly committed to career development of my trainees and others throughout the larger scientific community. With support of our work from NIH and private foundation grants, I have trained 15 Ph.D. students from diverse Yale Ph.D. programs (Genetics, Neuroscience, Molecular Biophysics and Biochemistry, M.D./Ph.D., Cell Biology, MCD-Biology), as well as 9 postdoctoral trainees, and all are still working scientists in an academia or industry.My trainees have gone on to Tenure Track/Staff Scientist positions in academia (Bar-Ilan University Medical School, Broad Institute/MIT, Emory, Hussman Institute/U. Maryland, U. Michigan, U. Nebraska, U. Texas-Southwestern, Old Dominion) or group leadership positions in Pharma/Biotech (Amgen, Caris Life Sciences, Constellation Pharmaceuticals). I am honored to serve as an active mentor for an exceptional group of trainees (6 predoctoral, 2 postdoctoral) currently in my lab. I also play an active role in science education. At Yale, I have participated in reworking how we teach introductory Biology, teaming with our partner departments (MCD-Biology, Ecology and Evolutionary Biology) to implement a unified first year biology curriculum. I also lead a graduate seminar in Molecular Biology and play various leadership roles in graduate education, currently serving as the Director of our combined BBS program. At the local level, I have hosted high school students to work in my lab and served as a judge for the Connecticut Science Olympiad. I have participated in the National Academies Summer Workshop on Science Education and adopted these best practices in the classroom. As a member of the ASCB Education Committee, I have organized symposia at the national meeting focusing on career development and promoting URM retention of undergraduate STEM majors. Finally, as member of the ASCB Public Policy Committee and Project 50, I have advocated for science and science funding. This has involved multiple advocacy meetings with U.S. Congress and Staff members on Capitol Hill, the annual “We Are Research” campaign during Nobel week, and encouraging letter writing to Congressional representatives.
Integrin ß1 signals through Arg to regulate postnatal dendritic arborization, synapse density, and behavior.
Warren, M.S., Gourley, S.L., Lin, Y.-C., Simpson, M.A., Taylor, J.R., Greer, C.A. and Koleske, A.J. (2012) Integrin ß1 signals through Arg to regulate postnatal dendritic arborization, synapse density, and behavior. J Neurosci. In press.
Arg kinase regulates prefrontal dendritic spine refinement and cocaine-induced plasticity.
Gourley, S.L., Olevska, A., Warren, M.S., Taylor, J., and Koleske, A.J. (2012) Arg kinase regulates prefrontal dendritic spine refinement and cocaine-induced plasticity. J Neurosci. In press.
- MacGrath, S.M. and Koleske, A.J. (2012) Cell Science at a glance: cortactin. J Cell Sci, In press.
An EGFR-Src-Arg-cortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion.
Mader, C.C., Oser, M., Magalhaes, M., *Condeelis, J., *Koleske, A.J., and Gil-Henn, H. (2011) EGF signaling through a Src-Arg-cortactin relay regulates breast cancer invasiveness by controlling invadopodia maturation and function. Cancer Research, 71(5):1730-41. *Corresponding Author
Mechanisms that promote long-term synapse and dendrite stability: disruption in psychiatric and neurodegenerative disorders.
Lin, Y.-C., and Koleske, A.J. (2010) Mechanisms that promote long-term synapse and dendrite stability: disruption in psychiatric and neurodegenerative disorders. Ann Rev Neurosci., 33:349-78.
Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine.
Gourley, S.L. Koleske, A.J., and Taylor, J.R. (2009) Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine. Proc. Natl. Acad. Sci. USA, 106(39):16859-64
Regulation of cell migration and morphogenesis by Abl family kinases: emerging mechanisms and physiological contexts.
Bradley, W.D., and Koleske, A.J. Regulation of cell migration and morphogenesis by Abl family kinases: emerging mechanisms and physiological contexts. (2009) J. Cell Sci, in press.
Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion.
Lapetina, S., Mader, C.C., Machida, K., Mayer, B.J., and Koleske, A.J. (2009) Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion. J. Cell Biol., 185: 503-19
Full List of PubMed Publications
- Katrancha SM, Wu Y, Zhu M, Eipper BA, Koleske AJ, Mains RE: Neurodevelopmental disease-associated de novo mutations and rare sequence variants affect TRIO GDP/GTP exchange factor activity. Hum Mol Genet. 2017 Sep 14; 2017 Sep 14. PMID: 28973398
- Thompson AD, Omar MH, Rivera-Molina F, Xi Z, Koleske AJ, Toomre DK, Schepartz A: Long-Term Live-Cell STED Nanoscopy of Primary and Cultured Cells with the Plasma Membrane HIDE Probe DiI-SiR. Angew Chem Int Ed Engl. 2017 Aug 21; 2017 Jul 24. PMID: 28679029
- Rosenberg BJ, Gil-Henn H, Mader CC, Halo T, Yin T, Condeelis J, Machida K, Wu YI, Koleske AJ: Phosphorylated cortactin recruits Vav2 guanine nucleotide exchange factor to activate Rac3 and promote invadopodial function in invasive breast cancer cells. Mol Biol Cell. 2017 May 15; 2017 Mar 29. PMID: 28356423
- Shapiro LP, Parsons RG, Koleske AJ, Gourley SL: Differential expression of cytoskeletal regulatory factors in the adolescent prefrontal cortex: Implications for cortical development. J Neurosci Res. 2017 May; 2016 Oct 13. PMID: 27735056
- Wetzel DM, Rhodes EL, Li S, McMahon-Pratt D, Koleske AJ: The Src kinases Hck, Fgr and Lyn activate Arg to facilitate IgG-mediated phagocytosis and Leishmania infection. J Cell Sci. 2016 Aug 15; 2016 Jun 29. PMID: 27358479
- Xiao X, Levy AD, Rosenberg BJ, Higley MJ, Koleske AJ: Disruption of Coordinated Presynaptic and Postsynaptic Maturation Underlies the Defects in Hippocampal Synapse Stability and Plasticity in Abl2/Arg-Deficient Mice. J Neurosci. 2016 Jun 22. PMID: 27335408
- Katrancha SM, Koleske AJ: SNARE Complex Dysfunction: A Unifying Hypothesis for Schizophrenia. Biol Psychiatry. 2015 Sep 15. PMID: 26296424
- Nygaard HB, Wagner AF, Bowen GS, Good SP, MacAvoy MG, Strittmatter KA, Kaufman AC, Rosenberg BJ, Sekine-Konno T, Varma P, Chen K, Koleske AJ, Reiman EM, Strittmatter SM, van Dyck CH: A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease. Alzheimers Res Ther. 2015; 2015 Apr 14. PMID: 25874001
- 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; 2015 Mar 20. PMID: 25849507
- Simpson MA, Bradley WD, Harburger D, Parsons M, Calderwood DA, Koleske AJ: Direct interactions with the integrin β1 cytoplasmic tail activate the Abl2/Arg kinase. J Biol Chem. 2015 Mar 27; 2015 Feb 18. PMID: 25694433
- Courtemanche N, Gifford SM, Simpson MA, Pollard TD, Koleske AJ: Abl2/Abl-related gene stabilizes actin filaments, stimulates actin branching by actin-related protein 2/3 complex, and promotes actin filament severing by cofilin. J Biol Chem. 2015 Feb 13; 2014 Dec 24. PMID: 25540195
- DePoy LM, Perszyk RE, Zimmermann KS, Koleske AJ, Gourley SL: Adolescent cocaine exposure simplifies orbitofrontal cortical dendritic arbors. Front Pharmacol. 2014; 2014 Oct 27. PMID: 25452728
- Levy AD, Omar MH, Koleske AJ: Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood. Front Neuroanat. 2014; 2014 Oct 20. PMID: 25368556
- Cooper MA, Koleske AJ: Ablation of ErbB4 from excitatory neurons leads to reduced dendritic spine density in mouse prefrontal cortex. J Comp Neurol. 2014 Oct 1; 2014 Apr 29. PMID: 24752666
- Gifford SM, Liu W, Mader CC, Halo TL, Machida K, Boggon TJ, Koleske AJ: Two amino acid residues confer different binding affinities of Abelson family kinase SRC homology 2 domains for phosphorylated cortactin. J Biol Chem. 2014 Jul 11; 2014 Jun 2. PMID: 24891505
- Kerrisk ME, Cingolani LA, Koleske AJ: ECM receptors in neuronal structure, synaptic plasticity, and behavior. Prog Brain Res. 2014. PMID: 25410355
- Kerrisk ME, Koleske AJ: Arg kinase signaling in dendrite and synapse stabilization pathways: memory, cocaine sensitivity, and stress. Int J Biochem Cell Biol. 2013 Nov; 2013 Aug 2. PMID: 23916785
- Um JW, Kaufman AC, Kostylev M, Heiss JK, Stagi M, Takahashi H, Kerrisk ME, Vortmeyer A, Wisniewski T, Koleske AJ, Gunther EC, Nygaard HB, Strittmatter SM: Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer aβ oligomer bound to cellular prion protein. Neuron. 2013 Sep 4. PMID: 24012003
- Koleske AJ: Molecular mechanisms of dendrite stability. Nat Rev Neurosci. 2013 Aug; 2013 Jul 10. PMID: 23839597
- Kerrisk ME, Greer CA, Koleske AJ: Integrin α3 is required for late postnatal stability of dendrite arbors, dendritic spines and synapses, and mouse behavior. J Neurosci. 2013 Apr 17. PMID: 23595732
- Couch BA, Kerrisk ME, Kaufman AC, Nygaard HB, Strittmatter SM, Koleske AJ: Delayed amyloid plaque deposition and behavioral deficits in outcrossed AβPP/PS1 mice. J Comp Neurol. 2013 Apr 15. PMID: 23047754
- Lin YC, Yeckel MF, Koleske AJ: Abl2/Arg controls dendritic spine and dendrite arbor stability via distinct cytoskeletal control pathways. J Neurosci. 2013 Jan 30. PMID: 23365224
- Deng Y, Couch BA, Koleske AJ, Turk BE: A peptide photoaffinity probe specific for the active conformation of the Abl tyrosine kinase. Chembiochem. 2012 Nov 26; 2012 Oct 18. PMID: 23081945
- MacGrath SM, Koleske AJ: Arg/Abl2 modulates the affinity and stoichiometry of binding of cortactin to F-actin. Biochemistry. 2012 Aug 21; 2012 Aug 10. PMID: 22849492
- Wetzel DM, McMahon-Pratt D, Koleske AJ: The Abl and Arg kinases mediate distinct modes of phagocytosis and are required for maximal Leishmania infection. Mol Cell Biol. 2012 Aug; 2012 Jun 4. PMID: 22665498
- MacGrath SM, Koleske AJ: Cortactin in cell migration and cancer at a glance. J Cell Sci. 2012 Apr 1. PMID: 22566665
- Warren MS, Bradley WD, Gourley SL, Lin YC, Simpson MA, Reichardt LF, Greer CA, Taylor JR, Koleske AJ: Integrin β1 signals through Arg to regulate postnatal dendritic arborization, synapse density, and behavior. J Neurosci. 2012 Feb 22. PMID: 22357865
- Gourley SL, Olevska A, Warren MS, Taylor JR, Koleske AJ: Arg kinase regulates prefrontal dendritic spine refinement and cocaine-induced plasticity. J Neurosci. 2012 Feb 15. PMID: 22396406
- Liu W, MacGrath SM, Koleske AJ, Boggon TJ: Lysozyme contamination facilitates crystallization of a heterotrimeric cortactin-Arg-lysozyme complex. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 Feb 1; 2012 Jan 25. PMID: 22297987
- Cooper MA, Koleske AJ: ErbB4 localization to interneurons: clearer insights into schizophrenia pathology. Biol Psychiatry. 2011 Oct 1. PMID: 21924131
- Chung C, Mader CC, Schmitz JC, Atladottir J, Fitchev P, Cornwell ML, Koleske AJ, Crawford SE, Gorelick F: The vacuolar-ATPase modulates matrix metalloproteinase isoforms in human pancreatic cancer. Lab Invest. 2011 May; 2011 Feb 21. PMID: 21339745
- MacGrath SM, Koleske AJ: Invadopodia: RhoC runs rings around cofilin. Curr Biol. 2011 Apr 26. PMID: 21514509
- Mader CC, Oser M, Magalhaes MA, Bravo-Cordero JJ, Condeelis J, Koleske AJ, Gil-Henn H: An EGFR-Src-Arg-cortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion. Cancer Res. 2011 Mar 1; 2011 Jan 21. PMID: 21257711
- Gourley SL, Taylor JR, Koleske AJ: Cell adhesion signaling pathways: First responders to cocaine exposure? Commun Integr Biol. 2011 Jan. PMID: 21509173
- Peacock JG, Couch BA, Koleske AJ: The Abl and Arg non-receptor tyrosine kinases regulate different zones of stress fiber, focal adhesion, and contractile network localization in spreading fibroblasts. Cytoskeleton (Hoboken). 2010 Oct. PMID: 20737438
- Miller MM, Lapetina S, MacGrath SM, Sfakianos MK, Pollard TD, Koleske AJ: Regulation of actin polymerization and adhesion-dependent cell edge protrusion by the Abl-related gene (Arg) tyrosine kinase and N-WASp. Biochemistry. 2010 Mar 16. PMID: 20146487
- Lin YC, Koleske AJ: Mechanisms of synapse and dendrite maintenance and their disruption in psychiatric and neurodegenerative disorders. Annu Rev Neurosci. 2010. PMID: 20367247
- Couch BA, DeMarco GJ, Gourley SL, Koleske AJ: Increased dendrite branching in AbetaPP/PS1 mice and elongation of dendrite arbors by fasudil administration. J Alzheimers Dis. 2010. PMID: 20413901
- Bradley WD, Koleske AJ: Regulation of cell migration and morphogenesis by Abl-family kinases: emerging mechanisms and physiological contexts. J Cell Sci. 2009 Oct 1. PMID: 19759284
- Gourley SL, Koleske AJ, Taylor JR: Loss of dendrite stabilization by the Abl-related gene (Arg) kinase regulates behavioral flexibility and sensitivity to cocaine. Proc Natl Acad Sci U S A. 2009 Sep 29; 2009 Sep 11. PMID: 19805386
- Lapetina S, Mader CC, Machida K, Mayer BJ, Koleske AJ: Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion. J Cell Biol. 2009 May 4. PMID: 19414610
- 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; 2007 Sep 25. PMID: 17892306
- Sfakianos MK, Eisman A, Gourley SL, Bradley WD, Scheetz AJ, Settleman J, Taylor JR, Greer CA, Williamson A, Koleske AJ: Inhibition of Rho via Arg and p190RhoGAP in the postnatal mouse hippocampus regulates dendritic spine maturation, synapse and dendrite stability, and behavior. J Neurosci. 2007 Oct 10. PMID: 17928439
- Peacock JG, Miller AL, Bradley WD, Rodriguez OC, Webb DJ, Koleske AJ: The Abl-related gene tyrosine kinase acts through p190RhoGAP to inhibit actomyosin contractility and regulate focal adhesion dynamics upon adhesion to fibronectin. Mol Biol Cell. 2007 Oct; 2007 Jul 25. PMID: 17652459
- Boyle SN, Koleske AJ: Dissecting kinase signaling pathways. Drug Discov Today. 2007 Sep; 2007 Aug 23. PMID: 17826684
- Boyle SN, Michaud GA, Schweitzer B, Predki PF, Koleske AJ: A critical role for cortactin phosphorylation by Abl-family kinases in PDGF-induced dorsal-wave formation. Curr Biol. 2007 Mar 6; 2007 Feb 15. PMID: 17306540
- 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; 2006 Sep 13. PMID: 16971514
- Moresco EM, Donaldson S, Williamson A, Koleske AJ: Integrin-mediated dendrite branch maintenance requires Abelson (Abl) family kinases. J Neurosci. 2005 Jun 29. PMID: 15987940
- Miller AL, Wang Y, Mooseker MS, Koleske AJ: The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion. J Cell Biol. 2004 May 10. PMID: 15138293
- Hernández SE, Settleman J, Koleske AJ: Adhesion-dependent regulation of p190RhoGAP in the developing brain by the Abl-related gene tyrosine kinase. Curr Biol. 2004 Apr 20. PMID: 15084284
- Hernández SE, Krishnaswami M, Miller AL, Koleske AJ: How do Abl family kinases regulate cell shape and movement? Trends Cell Biol. 2004 Jan. PMID: 14729179
- Moresco EM, Koleske AJ: Regulation of neuronal morphogenesis and synaptic function by Abl family kinases. Curr Opin Neurobiol. 2003 Oct. PMID: 14630215
- 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. PMID: 12748290
- Koleske AJ: Do filopodia enable the growth cone to find its way? Sci STKE. 2003 May 20; 2003 May 20. PMID: 12759482
- Moresco EM, Scheetz AJ, Bornmann WG, Koleske AJ, Fitzsimonds RM: Abl family nonreceptor tyrosine kinases modulate short-term synaptic plasticity. J Neurophysiol. 2003 Mar. PMID: 12626632