Skip to main content
NCBI home page
Molecular Biology of the Cell logoLink to Molecular Biology of the Cell
. 1995 Jun;6(6):661–674. doi: 10.1091/mbc.6.6.661

Specialized functional properties of the integrin alpha 4 cytoplasmic domain.

P D Kassner 1, R Alon 1, T A Springer 1, M E Hemler 1
PMCID: PMC301227  PMID: 7579686

Abstract

For functional studies of the integrin alpha 4 cytoplasmic domain, we have expressed the following in K562 and Chinese hamster ovary (CHO) cells: 1) wild-type alpha 4 (called X4C4), 2) two chimeric forms of alpha 4 (called X4C2 and X4C5) that contain the cytoplasmic domains of alpha 2 and alpha 5, respectively, and 3) alpha 4 with no cytoplasmic domain (X4C0). Cytoplasmic domain exchange had no effect on VLA-4-dependent static cell adhesion or tethering to VCAM-1 in conditions of shear flow. However, the presence of the alpha 2 or alpha 5 tails markedly enhanced VLA-4-dependent K562 cells spreading (X4C2 > X4C5 > X4C4 > X4C0), increased localization of VLA-4 into focal adhesion-like complexes in CHO cells (X4C2 > X4C5 > X4C4), and strengthened CHO and K562 cell resistance to detachment from VCAM-1 in conditions of shear flow (X4C2 > X4C5 > X4C4 > X4C0). Conversely, the alpha 4 tail supported greater VLA-4-dependent haptotactic and chemotactic cell migration. In the absence of any alpha tail (i.e., X4C0), robust focal adhesions were observed, even though cell spreading and adhesion strengthening were minimal. Thus, such focal adhesions may have relatively little functional importance, and should not be compared with focal adhesions formed when alpha tails are present. Together, these results indicate that all three alpha-chain tails exert defined positive effects (compared with no tail at all), but suggest that the alpha 4 cytoplasmic domain may be specialized to engage in weaker cytoskeletal interactions, leading to diminished focal adhesion formation, cell spreading, and adhesion strengthening, while augmenting cell migration and facilitating rolling under shear flow. These properties of the alpha 4 tail are consistent with the role of alpha 4 integrins on highly motile lymphocytes, monocytes, and eosinophils.

Full text

PDF
661

Images in this article

665Image
on p.665
666Image
on p.666
667Image
on p.667

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aiba S., Nakagawa S., Ozawa H., Miyake K., Yagita H., Tagami H. Up-regulation of alpha 4 integrin on activated Langerhans cells: analysis of adhesion molecules on Langerhans cells relating to their migration from skin to draining lymph nodes. J Invest Dermatol. 1993 Feb;100(2):143–147. doi: 10.1111/1523-1747.ep12462783. [DOI] [PubMed] [Google Scholar]
  2. Alon R., Kassner P. D., Carr M. W., Finger E. B., Hemler M. E., Springer T. A. The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. J Cell Biol. 1995 Mar;128(6):1243–1253. doi: 10.1083/jcb.128.6.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baron J. L., Madri J. A., Ruddle N. H., Hashim G., Janeway C. A., Jr Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med. 1993 Jan 1;177(1):57–68. doi: 10.1084/jem.177.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bauer J. S., Varner J., Schreiner C., Kornberg L., Nicholas R., Juliano R. L. Functional role of the cytoplasmic domain of the integrin alpha 5 subunit. J Cell Biol. 1993 Jul;122(1):209–221. doi: 10.1083/jcb.122.1.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berlin C., Berg E. L., Briskin M. J., Andrew D. P., Kilshaw P. J., Holzmann B., Weissman I. L., Hamann A., Butcher E. C. Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell. 1993 Jul 16;74(1):185–195. doi: 10.1016/0092-8674(93)90305-a. [DOI] [PubMed] [Google Scholar]
  6. Briesewitz R., Kern A., Marcantonio E. E. Ligand-dependent and -independent integrin focal contact localization: the role of the alpha chain cytoplasmic domain. Mol Biol Cell. 1993 Jun;4(6):593–604. doi: 10.1091/mbc.4.6.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burridge K., Fath K., Kelly T., Nuckolls G., Turner C. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu Rev Cell Biol. 1988;4:487–525. doi: 10.1146/annurev.cb.04.110188.002415. [DOI] [PubMed] [Google Scholar]
  8. Chan B. M., Elices M. J., Murphy E., Hemler M. E. Adhesion to vascular cell adhesion molecule 1 and fibronectin. Comparison of alpha 4 beta 1 (VLA-4) and alpha 4 beta 7 on the human B cell line JY. J Biol Chem. 1992 Apr 25;267(12):8366–8370. [PubMed] [Google Scholar]
  9. Chan B. M., Kassner P. D., Schiro J. A., Byers H. R., Kupper T. S., Hemler M. E. Distinct cellular functions mediated by different VLA integrin alpha subunit cytoplasmic domains. Cell. 1992 Mar 20;68(6):1051–1060. doi: 10.1016/0092-8674(92)90077-p. [DOI] [PubMed] [Google Scholar]
  10. Chan P. Y., Aruffo A. VLA-4 integrin mediates lymphocyte migration on the inducible endothelial cell ligand VCAM-1 and the extracellular matrix ligand fibronectin. J Biol Chem. 1993 Nov 25;268(33):24655–24664. [PubMed] [Google Scholar]
  11. Chen Y. P., O'Toole T. E., Shipley T., Forsyth J., LaFlamme S. E., Yamada K. M., Shattil S. J., Ginsberg M. H. "Inside-out" signal transduction inhibited by isolated integrin cytoplasmic domains. J Biol Chem. 1994 Jul 15;269(28):18307–18310. [PubMed] [Google Scholar]
  12. Chuluyan H. E., Issekutz A. C. VLA-4 integrin can mediate CD11/CD18-independent transendothelial migration of human monocytes. J Clin Invest. 1993 Dec;92(6):2768–2777. doi: 10.1172/JCI116895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Damle N. K., Klussman K., Leytze G., Aruffo A., Linsley P. S., Ledbetter J. A. Costimulation with integrin ligands intercellular adhesion molecule-1 or vascular cell adhesion molecule-1 augments activation-induced death of antigen-specific CD4+ T lymphocytes. J Immunol. 1993 Sep 1;151(5):2368–2379. [PubMed] [Google Scholar]
  14. Dunlevy J. R., Couchman J. R. Controlled induction of focal adhesion disassembly and migration in primary fibroblasts. J Cell Sci. 1993 Jun;105(Pt 2):489–500. doi: 10.1242/jcs.105.2.489. [DOI] [PubMed] [Google Scholar]
  15. Elices M. J., Osborn L., Takada Y., Crouse C., Luhowskyj S., Hemler M. E., Lobb R. R. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell. 1990 Feb 23;60(4):577–584. doi: 10.1016/0092-8674(90)90661-w. [DOI] [PubMed] [Google Scholar]
  16. Freedman A. S., Rhynhart K., Nojima Y., Svahn J., Eliseo L., Benjamin C. D., Morimoto C., Vivier E. Stimulation of protein tyrosine phosphorylation in human B cells after ligation of the beta 1 integrin VLA-4. J Immunol. 1993 Mar 1;150(5):1645–1652. [PubMed] [Google Scholar]
  17. Garcia-Pardo A., Ferreira O. C. Adhesion of human T-lymphoid cells to fibronectin is mediated by two different fibronectin domains. Immunology. 1990 Jan;69(1):121–126. [PMC free article] [PubMed] [Google Scholar]
  18. Garcia-Pardo A., Rostagno A., Frangione B. Primary structure of human plasma fibronectin. Characterization of a 38 kDa domain containing the C-terminal heparin-binding site (Hep III site) and a region of molecular heterogeneity. Biochem J. 1987 Feb 1;241(3):923–928. doi: 10.1042/bj2410923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Giancotti F. G., Ruoslahti E. Elevated levels of the alpha 5 beta 1 fibronectin receptor suppress the transformed phenotype of Chinese hamster ovary cells. Cell. 1990 Mar 9;60(5):849–859. doi: 10.1016/0092-8674(90)90098-y. [DOI] [PubMed] [Google Scholar]
  20. Grzesiak J. J., Davis G. E., Kirchhofer D., Pierschbacher M. D. Regulation of alpha 2 beta 1-mediated fibroblast migration on type I collagen by shifts in the concentrations of extracellular Mg2+ and Ca2+. J Cell Biol. 1992 Jun;117(5):1109–1117. doi: 10.1083/jcb.117.5.1109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Guan J. L., Hynes R. O. Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1. Cell. 1990 Jan 12;60(1):53–61. doi: 10.1016/0092-8674(90)90715-q. [DOI] [PubMed] [Google Scholar]
  22. Hemler M. E., Huang C., Takada Y., Schwarz L., Strominger J. L., Clabby M. L. Characterization of the cell surface heterodimer VLA-4 and related peptides. J Biol Chem. 1987 Aug 25;262(24):11478–11485. [PubMed] [Google Scholar]
  23. Hemler M. E., Strominger J. L. Monoclonal antibodies reacting with immunogenic mycoplasma proteins present in human hematopoietic cell lines. J Immunol. 1982 Dec;129(6):2734–2738. [PubMed] [Google Scholar]
  24. Issekutz T. B. Inhibition of in vivo lymphocyte migration to inflammation and homing to lymphoid tissues by the TA-2 monoclonal antibody. A likely role for VLA-4 in vivo. J Immunol. 1991 Dec 15;147(12):4178–4184. [PubMed] [Google Scholar]
  25. Kassner P. D., Hemler M. E. Interchangeable alpha chain cytoplasmic domains play a positive role in control of cell adhesion mediated by VLA-4, a beta 1 integrin. J Exp Med. 1993 Aug 1;178(2):649–660. doi: 10.1084/jem.178.2.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kassner P. D., Kawaguchi S., Hemler M. E. Minimum alpha chain cytoplasmic tail sequence needed to support integrin-mediated adhesion. J Biol Chem. 1994 Aug 5;269(31):19859–19867. [PubMed] [Google Scholar]
  27. Kawaguchi S., Bergelson J. M., Finberg R. W., Hemler M. E. Integrin alpha 2 cytoplasmic domain deletion effects: loss of adhesive activity parallels ligand-independent recruitment into focal adhesions. Mol Biol Cell. 1994 Sep;5(9):977–988. doi: 10.1091/mbc.5.9.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kawaguchi S., Hemler M. E. Role of the alpha subunit cytoplasmic domain in regulation of adhesive activity mediated by the integrin VLA-2. J Biol Chem. 1993 Aug 5;268(22):16279–16285. [PubMed] [Google Scholar]
  29. Koopman G., Keehnen R. M., Lindhout E., Newman W., Shimizu Y., van Seventer G. A., de Groot C., Pals S. T. Adhesion through the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and the VLA-4 (CD49d)-VCAM-1 (CD106) pathways prevents apoptosis of germinal center B cells. J Immunol. 1994 Apr 15;152(8):3760–3767. [PubMed] [Google Scholar]
  30. LaFlamme S. E., Akiyama S. K., Yamada K. M. Regulation of fibronectin receptor distribution. J Cell Biol. 1992 Apr;117(2):437–447. doi: 10.1083/jcb.117.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. LaFlamme S. E., Thomas L. A., Yamada S. S., Yamada K. M. Single subunit chimeric integrins as mimics and inhibitors of endogenous integrin functions in receptor localization, cell spreading and migration, and matrix assembly. J Cell Biol. 1994 Sep;126(5):1287–1298. doi: 10.1083/jcb.126.5.1287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Lawrence M. B., Springer T. A. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859–873. doi: 10.1016/0092-8674(91)90393-d. [DOI] [PubMed] [Google Scholar]
  33. Leavesley D. I., Schwartz M. A., Rosenfeld M., Cheresh D. A. Integrin beta 1- and beta 3-mediated endothelial cell migration is triggered through distinct signaling mechanisms. J Cell Biol. 1993 Apr;121(1):163–170. doi: 10.1083/jcb.121.1.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lobb R., Chi-Rosso G., Leone D., Rosa M., Newman B., Luhowskyj S., Osborn L., Schiffer S., Benjamin C., Dougas I. Expression and functional characterization of a soluble form of vascular cell adhesion molecule 1. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1498–1504. doi: 10.1016/0006-291x(91)91063-i. [DOI] [PubMed] [Google Scholar]
  35. Lukashev M. E., Sheppard D., Pytela R. Disruption of integrin function and induction of tyrosine phosphorylation by the autonomously expressed beta 1 integrin cytoplasmic domain. J Biol Chem. 1994 Jul 15;269(28):18311–18314. [PubMed] [Google Scholar]
  36. Marcantonio E. E., Guan J. L., Trevithick J. E., Hynes R. O. Mapping of the functional determinants of the integrin beta 1 cytoplasmic domain by site-directed mutagenesis. Cell Regul. 1990 Jul;1(8):597–604. doi: 10.1091/mbc.1.8.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Miyake K., Hasunuma Y., Yagita H., Kimoto M. Requirement for VLA-4 and VLA-5 integrins in lymphoma cells binding to and migration beneath stromal cells in culture. J Cell Biol. 1992 Nov;119(3):653–662. doi: 10.1083/jcb.119.3.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mueller S. C., Kelly T., Dai M. Z., Dai H. N., Chen W. T. Dynamic cytoskeleton-integrin associations induced by cell binding to immobilized fibronectin. J Cell Biol. 1989 Dec;109(6 Pt 2):3455–3464. doi: 10.1083/jcb.109.6.3455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Nojima Y., Rothstein D. M., Sugita K., Schlossman S. F., Morimoto C. Ligation of VLA-4 on T cells stimulates tyrosine phosphorylation of a 105-kD protein. J Exp Med. 1992 Apr 1;175(4):1045–1053. doi: 10.1084/jem.175.4.1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. O'Toole T. E., Katagiri Y., Faull R. J., Peter K., Tamura R., Quaranta V., Loftus J. C., Shattil S. J., Ginsberg M. H. Integrin cytoplasmic domains mediate inside-out signal transduction. J Cell Biol. 1994 Mar;124(6):1047–1059. doi: 10.1083/jcb.124.6.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. O'Toole T. E., Mandelman D., Forsyth J., Shattil S. J., Plow E. F., Ginsberg M. H. Modulation of the affinity of integrin alpha IIb beta 3 (GPIIb-IIIa) by the cytoplasmic domain of alpha IIb. Science. 1991 Nov 8;254(5033):845–847. doi: 10.1126/science.1948065. [DOI] [PubMed] [Google Scholar]
  42. Papayannopoulou T., Nakamoto B. Peripheralization of hemopoietic progenitors in primates treated with anti-VLA4 integrin. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9374–9378. doi: 10.1073/pnas.90.20.9374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Pasqualini R., Hemler M. E. Contrasting roles for integrin beta 1 and beta 5 cytoplasmic domains in subcellular localization, cell proliferation, and cell migration. J Cell Biol. 1994 Apr;125(2):447–460. doi: 10.1083/jcb.125.2.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Plopper G., Ingber D. E. Rapid induction and isolation of focal adhesion complexes. Biochem Biophys Res Commun. 1993 Jun 15;193(2):571–578. doi: 10.1006/bbrc.1993.1662. [DOI] [PubMed] [Google Scholar]
  45. Qian F., Vaux D. L., Weissman I. L. Expression of the integrin alpha 4 beta 1 on melanoma cells can inhibit the invasive stage of metastasis formation. Cell. 1994 May 6;77(3):335–347. doi: 10.1016/0092-8674(94)90149-x. [DOI] [PubMed] [Google Scholar]
  46. Reszka A. A., Hayashi Y., Horwitz A. F. Identification of amino acid sequences in the integrin beta 1 cytoplasmic domain implicated in cytoskeletal association. J Cell Biol. 1992 Jun;117(6):1321–1330. doi: 10.1083/jcb.117.6.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Rice G. E., Bevilacqua M. P. An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science. 1989 Dec 8;246(4935):1303–1306. doi: 10.1126/science.2588007. [DOI] [PubMed] [Google Scholar]
  48. Rice G. E., Munro J. M., Bevilacqua M. P. Inducible cell adhesion molecule 110 (INCAM-110) is an endothelial receptor for lymphocytes. A CD11/CD18-independent adhesion mechanism. J Exp Med. 1990 Apr 1;171(4):1369–1374. doi: 10.1084/jem.171.4.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Rogers B. B., Josephson S. L., Mak S. K. Detection of herpes simplex virus using the polymerase chain reaction followed by endonuclease cleavage. Am J Pathol. 1991 Jul;139(1):1–6. [PMC free article] [PubMed] [Google Scholar]
  50. Romanic A. M., Madri J. A. The induction of 72-kD gelatinase in T cells upon adhesion to endothelial cells is VCAM-1 dependent. J Cell Biol. 1994 Jun;125(5):1165–1178. doi: 10.1083/jcb.125.5.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Rosen G. D., Sanes J. R., LaChance R., Cunningham J. M., Roman J., Dean D. C. Roles for the integrin VLA-4 and its counter receptor VCAM-1 in myogenesis. Cell. 1992 Jun 26;69(7):1107–1119. doi: 10.1016/0092-8674(92)90633-n. [DOI] [PubMed] [Google Scholar]
  52. Rüegg C., Postigo A. A., Sikorski E. E., Butcher E. C., Pytela R., Erle D. J. Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering. J Cell Biol. 1992 Apr;117(1):179–189. doi: 10.1083/jcb.117.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Sastry S. K., Horwitz A. F. Integrin cytoplasmic domains: mediators of cytoskeletal linkages and extra- and intracellular initiated transmembrane signaling. Curr Opin Cell Biol. 1993 Oct;5(5):819–831. doi: 10.1016/0955-0674(93)90031-k. [DOI] [PubMed] [Google Scholar]
  54. Schreiner C. L., Bauer J. S., Danilov Y. N., Hussein S., Sczekan M. M., Juliano R. L. Isolation and characterization of Chinese hamster ovary cell variants deficient in the expression of fibronectin receptor. J Cell Biol. 1989 Dec;109(6 Pt 1):3157–3167. doi: 10.1083/jcb.109.6.3157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Schwartz B. R., Wayner E. A., Carlos T. M., Ochs H. D., Harlan J. M. Identification of surface proteins mediating adherence of CD11/CD18-deficient lymphoblastoid cells to cultured human endothelium. J Clin Invest. 1990 Jun;85(6):2019–2022. doi: 10.1172/JCI114668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Sheppard A. M., Onken M. D., Rosen G. D., Noakes P. G., Dean D. C. Expanding roles for alpha 4 integrin and its ligands in development. Cell Adhes Commun. 1994 Apr;2(1):27–43. doi: 10.3109/15419069409014200. [DOI] [PubMed] [Google Scholar]
  57. Smilenov L., Briesewitz R., Marcantonio E. E. Integrin beta 1 cytoplasmic domain dominant negative effects revealed by lysophosphatidic acid treatment. Mol Biol Cell. 1994 Nov;5(11):1215–1223. doi: 10.1091/mbc.5.11.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Stepp M. A., Urry L. A., Hynes R. O. Expression of alpha 4 integrin mRNA and protein and fibronectin in the early chicken embryo. Cell Adhes Commun. 1994 Aug;2(4):359–375. doi: 10.3109/15419069409014210. [DOI] [PubMed] [Google Scholar]
  59. Sánchez-Madrid F., De Landázuri M. O., Morago G., Cebrián M., Acevedo A., Bernabeu C. VLA-3: a novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization. Eur J Immunol. 1986 Nov;16(11):1343–1349. doi: 10.1002/eji.1830161106. [DOI] [PubMed] [Google Scholar]
  60. Wayner E. A., Garcia-Pardo A., Humphries M. J., McDonald J. A., Carter W. G. Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin. J Cell Biol. 1989 Sep;109(3):1321–1330. doi: 10.1083/jcb.109.3.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Williams D. A., Rios M., Stephens C., Patel V. P. Fibronectin and VLA-4 in haematopoietic stem cell-microenvironment interactions. Nature. 1991 Aug 1;352(6334):438–441. doi: 10.1038/352438a0. [DOI] [PubMed] [Google Scholar]
  62. Woods A., McCarthy J. B., Furcht L. T., Couchman J. R. A synthetic peptide from the COOH-terminal heparin-binding domain of fibronectin promotes focal adhesion formation. Mol Biol Cell. 1993 Jun;4(6):605–613. doi: 10.1091/mbc.4.6.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Yamada K. M., Kennedy D. W., Yamada S. S., Gralnick H., Chen W. T., Akiyama S. K. Monoclonal antibody and synthetic peptide inhibitors of human tumor cell migration. Cancer Res. 1990 Aug 1;50(15):4485–4496. [PubMed] [Google Scholar]
  64. Yednock T. A., Cannon C., Fritz L. C., Sanchez-Madrid F., Steinman L., Karin N. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature. 1992 Mar 5;356(6364):63–66. doi: 10.1038/356063a0. [DOI] [PubMed] [Google Scholar]
  65. Ylänne J., Chen Y., O'Toole T. E., Loftus J. C., Takada Y., Ginsberg M. H. Distinct functions of integrin alpha and beta subunit cytoplasmic domains in cell spreading and formation of focal adhesions. J Cell Biol. 1993 Jul;122(1):223–233. doi: 10.1083/jcb.122.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Yurochko A. D., Liu D. Y., Eierman D., Haskill S. Integrins as a primary signal transduction molecule regulating monocyte immediate-early gene induction. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9034–9038. doi: 10.1073/pnas.89.19.9034. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular Biology of the Cell are provided here courtesy of American Society for Cell Biology

RESOURCES