Search tips
Search criteria 


Logo of jcellbiolHomeEditorsContactInstructions for Authors
J Cell Biol. 1994 February 1; 124(3): 325–340.
PMCID: PMC2119935

The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin binding domains with bundling activity [published erratum appears in J Cell Biol 1994 Mar;124(5):865]


The myristoylated form of c-Abl protein, as well as the P210bcr/abl protein, have been shown by indirect immunofluorescence to associate with F-actin stress fibers in fibroblasts. Analysis of deletion mutants of c-Abl stably expressed in fibroblasts maps the domain responsible for this interaction to the extreme COOH-terminus of Abl. This domain mediates the association of a heterologous protein with F-actin filaments after microinjection into NIH 3T3 cells, and directly binds to F-actin in a cosedimentation assay. Microinjection and cosedimentation assays localize the actin-binding domain to a 58 amino acid region, including a charged motif at the extreme COOH-terminus that is important for efficient binding. F-actin binding by Abl is calcium independent, and Abl competes with gelsolin for binding to F- actin. In addition to the F-actin binding domain, the COOH-terminus of Abl contains a proline-rich region that mediates binding and sequestration of G-actin, and the Abl F- and G-actin binding domains cooperate to bundle F-actin filaments in vitro. The COOH terminus of Abl thus confers several novel localizing functions upon the protein, including actin binding, nuclear localization, and DNA binding. Abl may modify and receive signals from the F-actin cytoskeleton in vivo, and is an ideal candidate to mediate signal transduction from the cell surface and cytoskeleton to the nucleus.

Full Text

The Full Text of this article is available as a PDF (4.9M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Adams AE, Botstein D, Drubin DG. Requirement of yeast fimbrin for actin organization and morphogenesis in vivo. Nature. 1991 Dec 5;354(6352):404–408. [PubMed]
  • Bar-Sagi D, Rotin D, Batzer A, Mandiyan V, Schlessinger J. SH3 domains direct cellular localization of signaling molecules. Cell. 1993 Jul 16;74(1):83–91. [PubMed]
  • Ben-Neriah Y, Bernards A, Paskind M, Daley GQ, Baltimore D. Alternative 5' exons in c-abl mRNA. Cell. 1986 Feb 28;44(4):577–586. [PubMed]
  • Bryan J. Gelsolin has three actin-binding sites. J Cell Biol. 1988 May;106(5):1553–1562. [PMC free article] [PubMed]
  • Campbell ML, Li W, Arlinghaus RB. P210 BCR-ABL is complexed to P160 BCR and ph-P53 proteins in K562 cells. Oncogene. 1990 May;5(5):773–776. [PubMed]
  • Carlier MF, Jean C, Rieger KJ, Lenfant M, Pantaloni D. Modulation of the interaction between G-actin and thymosin beta 4 by the ATP/ADP ratio: possible implication in the regulation of actin dynamics. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5034–5038. [PubMed]
  • Cicchetti P, Mayer BJ, Thiel G, Baltimore D. Identification of a protein that binds to the SH3 region of Abl and is similar to Bcr and GAP-rho. Science. 1992 Aug 7;257(5071):803–806. [PubMed]
  • Daley GQ, Van Etten RA, Jackson PK, Bernards A, Baltimore D. Nonmyristoylated Abl proteins transform a factor-dependent hematopoietic cell line. Mol Cell Biol. 1992 Apr;12(4):1864–1871. [PMC free article] [PubMed]
  • Detmers P, Weber A, Elzinga M, Stephens RE. 7-Chloro-4-nitrobenzeno-2-oxa-1,3-diazole actin as a probe for actin polymerization. J Biol Chem. 1981 Jan 10;256(1):99–105. [PubMed]
  • Drubin DG, Mulholland J, Zhu ZM, Botstein D. Homology of a yeast actin-binding protein to signal transduction proteins and myosin-I. Nature. 1990 Jan 18;343(6255):288–290. [PubMed]
  • Gertler FB, Bennett RL, Clark MJ, Hoffmann FM. Drosophila abl tyrosine kinase in embryonic CNS axons: a role in axonogenesis is revealed through dosage-sensitive interactions with disabled. Cell. 1989 Jul 14;58(1):103–113. [PubMed]
  • Glenney JR, Jr, Kaulfus P, Matsudaira P, Weber K. F-actin binding and bundling properties of fimbrin, a major cytoskeletal protein of microvillus core filaments. J Biol Chem. 1981 Sep 10;256(17):9283–9288. [PubMed]
  • Goldschmidt-Clermont PJ, Furman MI, Wachsstock D, Safer D, Nachmias VT, Pollard TD. The control of actin nucleotide exchange by thymosin beta 4 and profilin. A potential regulatory mechanism for actin polymerization in cells. Mol Biol Cell. 1992 Sep;3(9):1015–1024. [PMC free article] [PubMed]
  • Graessmann A, Graessmann M, Mueller C. Microinjection of early SV40 DNA fragments and T antigen. Methods Enzymol. 1980;65(1):816–825. [PubMed]
  • Hartwig JH, Thelen M, Rosen A, Janmey PA, Nairn AC, Aderem A. MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin. Nature. 1992 Apr 16;356(6370):618–622. [PubMed]
  • Hemmings L, Kuhlman PA, Critchley DR. Analysis of the actin-binding domain of alpha-actinin by mutagenesis and demonstration that dystrophin contains a functionally homologous domain. J Cell Biol. 1992 Mar;116(6):1369–1380. [PMC free article] [PubMed]
  • Henkemeyer M, West SR, Gertler FB, Hoffmann FM. A novel tyrosine kinase-independent function of Drosophila abl correlates with proper subcellular localization. Cell. 1990 Nov 30;63(5):949–960. [PubMed]
  • Horvitz HR, Sternberg PW. Multiple intercellular signalling systems control the development of the Caenorhabditis elegans vulva. Nature. 1991 Jun 13;351(6327):535–541. [PubMed]
  • Howard PK, Sefton BM, Firtel RA. Tyrosine phosphorylation of actin in Dictyostelium associated with cell-shape changes. Science. 1993 Jan 8;259(5092):241–244. [PubMed]
  • Hynes RO. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. [PubMed]
  • Jackson P, Baltimore D. N-terminal mutations activate the leukemogenic potential of the myristoylated form of c-abl. EMBO J. 1989 Feb;8(2):449–456. [PubMed]
  • Ji X, Zhang P, Armstrong RN, Gilliland GL. The three-dimensional structure of a glutathione S-transferase from the mu gene class. Structural analysis of the binary complex of isoenzyme 3-3 and glutathione at 2.2-A resolution. Biochemistry. 1992 Oct 27;31(42):10169–10184. [PubMed]
  • Jung G, Korn ED, Hammer JA., 3rd The heavy chain of Acanthamoeba myosin IB is a fusion of myosin-like and non-myosin-like sequences. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6720–6724. [PubMed]
  • Kamps MP, Buss JE, Sefton BM. Rous sarcoma virus transforming protein lacking myristic acid phosphorylates known polypeptide substrates without inducing transformation. Cell. 1986 Apr 11;45(1):105–112. [PubMed]
  • Kaplan JM, Varmus HE, Bishop JM. The src protein contains multiple domains for specific attachment to membranes. Mol Cell Biol. 1990 Mar;10(3):1000–1009. [PMC free article] [PubMed]
  • Kipreos ET, Wang JY. Cell cycle-regulated binding of c-Abl tyrosine kinase to DNA. Science. 1992 Apr 17;256(5055):382–385. [PubMed]
  • Klarlund JK. Transformation of cells by an inhibitor of phosphatases acting on phosphotyrosine in proteins. Cell. 1985 Jul;41(3):707–717. [PubMed]
  • Konopka JB, Davis RL, Watanabe SM, Ponticelli AS, Schiff-Maker L, Rosenberg N, Witte ON. Only site-directed antibodies reactive with the highly conserved src-homologous region of the v-abl protein neutralize kinase activity. J Virol. 1984 Jul;51(1):223–232. [PMC free article] [PubMed]
  • Kouyama T, Mihashi K. Fluorimetry study of N-(1-pyrenyl)iodoacetamide-labelled F-actin. Local structural change of actin protomer both on polymerization and on binding of heavy meromyosin. Eur J Biochem. 1981;114(1):33–38. [PubMed]
  • Krueger JG, Garber EA, Goldberg AR, Hanafusa H. Changes in amino-terminal sequences of pp60src lead to decreased membrane association and decreased in vivo tumorigenicity. Cell. 1982 Apr;28(4):889–896. [PubMed]
  • Kruh GD, Perego R, Miki T, Aaronson SA. The complete coding sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5802–5806. [PubMed]
  • Laham LE, Lamb JA, Allen PG, Janmey PA. Selective binding of gelsolin to actin monomers containing ADP. J Biol Chem. 1993 Jul 5;268(19):14202–14207. [PubMed]
  • Lal AA, Korn ED. Reinvestigation of the inhibition of actin polymerization by profilin. J Biol Chem. 1985 Aug 25;260(18):10132–10138. [PubMed]
  • Lee S, Li M, Pollard TD. Evaluation of the binding of Acanthamoeba profilin to pyrene-labeled actin by fluorescence enhancement. Anal Biochem. 1988 Jan;168(1):148–155. [PubMed]
  • Lynch WP, Riseman VM, Bretscher A. Smooth muscle caldesmon is an extended flexible monomeric protein in solution that can readily undergo reversible intra- and intermolecular sulfhydryl cross-linking. A mechanism for caldesmon's F-actin bundling activity. J Biol Chem. 1987 May 25;262(15):7429–7437. [PubMed]
  • MacLean-Fletcher S, Pollard TD. Identification of a factor in conventional muscle actin preparations which inhibits actin filament self-association. Biochem Biophys Res Commun. 1980 Sep 16;96(1):18–27. [PubMed]
  • Matsudaira P. Modular organization of actin crosslinking proteins. Trends Biochem Sci. 1991 Mar;16(3):87–92. [PubMed]
  • Matsudaira PT, Burgess DR. SDS microslab linear gradient polyacrylamide gel electrophoresis. Anal Biochem. 1978 Jul 1;87(2):386–396. [PubMed]
  • Matsudaira P, Janmey P. Pieces in the actin-severing protein puzzle. Cell. 1988 Jul 15;54(2):139–140. [PubMed]
  • Matsudaira PT. Structural and functional relationship between the membrane and the cytoskeleton in brush border microvilli. Ciba Found Symp. 1983;95:233–252. [PubMed]
  • Mayer BJ, Jackson PK, Van Etten RA, Baltimore D. Point mutations in the abl SH2 domain coordinately impair phosphotyrosine binding in vitro and transforming activity in vivo. Mol Cell Biol. 1992 Feb;12(2):609–618. [PMC free article] [PubMed]
  • Muller AJ, Young JC, Pendergast AM, Pondel M, Landau NR, Littman DR, Witte ON. BCR first exon sequences specifically activate the BCR/ABL tyrosine kinase oncogene of Philadelphia chromosome-positive human leukemias. Mol Cell Biol. 1991 Apr;11(4):1785–1792. [PMC free article] [PubMed]
  • McWhirter JR, Wang JY. An actin-binding function contributes to transformation by the Bcr-Abl oncoprotein of Philadelphia chromosome-positive human leukemias. EMBO J. 1993 Apr;12(4):1533–1546. [PubMed]
  • Parker MW, Lo Bello M, Federici G. Crystallization of glutathione S-transferase from human placenta. J Mol Biol. 1990 May 20;213(2):221–222. [PubMed]
  • Pendergast AM, Traugh JA, Witte ON. Normal cellular and transformation-associated abl proteins share common sites for protein kinase C phosphorylation. Mol Cell Biol. 1987 Dec;7(12):4280–4289. [PMC free article] [PubMed]
  • Prywes R, Foulkes JG, Baltimore D. The minimum transforming region of v-abl is the segment encoding protein-tyrosine kinase. J Virol. 1985 Apr;54(1):114–122. [PMC free article] [PubMed]
  • Ren R, Mayer BJ, Cicchetti P, Baltimore D. Identification of a ten-amino acid proline-rich SH3 binding site. Science. 1993 Feb 19;259(5098):1157–1161. [PubMed]
  • Ridley AJ, Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 1992 Aug 7;70(3):389–399. [PubMed]
  • Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 1992 Aug 7;70(3):401–410. [PubMed]
  • Rohrschneider LR. Adhesion plaques of Rous sarcoma virus-transformed cells contain the src gene product. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3514–3518. [PubMed]
  • Rohrschneider LR, Najita LM. Detection of the v-abl gene product at cell-substratum contact sites in Abelson murine leukemia virus-transformed fibroblasts. J Virol. 1984 Aug;51(2):547–552. [PMC free article] [PubMed]
  • Safer D. An electrophoretic procedure for detecting proteins that bind actin monomers. Anal Biochem. 1989 Apr;178(1):32–37. [PubMed]
  • Sanders MC, Goldstein AL, Wang YL. Thymosin beta 4 (Fx peptide) is a potent regulator of actin polymerization in living cells. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4678–4682. [PubMed]
  • Schliwa M, van Blerkom J. Structural interaction of cytoskeletal components. J Cell Biol. 1981 Jul;90(1):222–235. [PMC free article] [PubMed]
  • Schwartzberg PL, Stall AM, Hardin JD, Bowdish KS, Humaran T, Boast S, Harbison ML, Robertson EJ, Goff SP. Mice homozygous for the ablm1 mutation show poor viability and depletion of selected B and T cell populations. Cell. 1991 Jun 28;65(7):1165–1175. [PubMed]
  • Schweiger A, Mihalache O, Ecke M, Gerisch G. Stage-specific tyrosine phosphorylation of actin in Dictyostelium discoideum cells. J Cell Sci. 1992 Jul;102(Pt 3):601–609. [PubMed]
  • Simon MA, Dodson GS, Rubin GM. An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro. Cell. 1993 Apr 9;73(1):169–177. [PubMed]
  • Small JV, Isenberg G, Celis JE. Polarity of actin at the leading edge of cultured cells. Nature. 1978 Apr 13;272(5654):638–639. [PubMed]
  • Spudich JA, Watt S. The regulation of rabbit skeletal muscle contraction. I. Biochemical studies of the interaction of the tropomyosin-troponin complex with actin and the proteolytic fragments of myosin. J Biol Chem. 1971 Aug 10;246(15):4866–4871. [PubMed]
  • Studier FW, Rosenberg AH, Dunn JJ, Dubendorff JW. Use of T7 RNA polymerase to direct expression of cloned genes. Methods Enzymol. 1990;185:60–89. [PubMed]
  • Tellam RL, Morton DJ, Clarke FM. A common theme in the amino acid sequences of actin and many actin-binding proteins? Trends Biochem Sci. 1989 Apr;14(4):130–133. [PubMed]
  • Tybulewicz VL, Crawford CE, Jackson PK, Bronson RT, Mulligan RC. Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell. 1991 Jun 28;65(7):1153–1163. [PubMed]
  • Van Etten RA, Jackson P, Baltimore D. The mouse type IV c-abl gene product is a nuclear protein, and activation of transforming ability is associated with cytoplasmic localization. Cell. 1989 Aug 25;58(4):669–678. [PubMed]
  • Vandekerckhove J. Structural principles of actin-binding proteins. Curr Opin Cell Biol. 1989 Feb;1(1):15–22. [PubMed]
  • Vandekerckhove J, Bauw G, Vancompernolle K, Honoré B, Celis J. Comparative two-dimensional gel analysis and microsequencing identifies gelsolin as one of the most prominent downregulated markers of transformed human fibroblast and epithelial cells. J Cell Biol. 1990 Jul;111(1):95–102. [PMC free article] [PubMed]
  • Wang N, Butler JP, Ingber DE. Mechanotransduction across the cell surface and through the cytoskeleton. Science. 1993 May 21;260(5111):1124–1127. [PubMed]
  • Wasenius VM, Saraste M, Salvén P, Erämaa M, Holm L, Lehto VP. Primary structure of the brain alpha-spectrin. J Cell Biol. 1989 Jan;108(1):79–93. [PMC free article] [PubMed]
  • Way M, Pope B, Weeds AG. Are the conserved sequences in segment 1 of gelsolin important for binding actin? J Cell Biol. 1992 Mar;116(5):1135–1143. [PMC free article] [PubMed]
  • Way M, Pope B, Weeds AG. Evidence for functional homology in the F-actin binding domains of gelsolin and alpha-actinin: implications for the requirements of severing and capping. J Cell Biol. 1992 Nov;119(4):835–842. [PMC free article] [PubMed]
  • Wetzler M, Talpaz M, Van Etten RA, Hirsh-Ginsberg C, Beran M, Kurzrock R. Subcellular localization of Bcr, Abl, and Bcr-Abl proteins in normal and leukemic cells and correlation of expression with myeloid differentiation. J Clin Invest. 1993 Oct;92(4):1925–1939. [PMC free article] [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press