Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1993 Nov 1;123(3):549–560. doi: 10.1083/jcb.123.3.549

The v-sis protein retains biological activity as a type II membrane protein when anchored by various signal-anchor domains, including the hydrophobic domain of the bovine papilloma virus E5 oncoprotein

PMCID: PMC2200122  PMID: 8227125

Abstract

Membrane-anchored forms of the v-sis oncoprotein have been previously described which are oriented as type I transmembrane proteins and which efficiently induce autocrine transformation. Several examples of naturally occurring membrane-anchored growth factors have been identified, but all exhibit a type I orientation. In this work, we wished to construct and characterize membrane-anchored growth factors with a type II orientation. These experiments were designed to determine whether type II membrane-anchored growth factors would in fact exhibit biological activity. Additionally, we wished to determine whether the hydrophobic domain of the E5 oncoprotein of bovine papilloma virus (BPV) can function as a signal-anchor domain to direct type II membrane insertion. Type II derivatives of the v-sis oncoprotein were constructed, with the NH2 terminus intracellular and the COOH terminus extracellular, by substituting the NH2 terminal signal sequence with the signal-anchor domain of a known type II membrane protein. The signal-anchor domains of neuraminidase (NA), asialoglycoprotein receptor (ASGPR) and transferrin receptor (TR) all yielded biologically active type II derivatives of the v-sis oncoprotein. Although transforming all of the type II signal/anchor-sis proteins exhibited a very short half-life. The short half-life exhibited by the signal/anchor-sis constructs suggests that, in some cases, cellular transformation may result from the synthesis of growth factors so labile that they activate undetectable autocrine loops. The E5 oncoprotein encoded by BPV exhibits amino acid sequence similarity with PDGF, activates the PDGF beta-receptor, and thus resembles a miniature membrane-anchored growth factor with a putative type II orientation. The hydrophobic domain of the E5 oncoprotein, when substituted in place of the signal sequence of v-sis, was indistinguishable compared with the signal-anchor domains of NA, TR, and ASGPR, demonstrating its ability to function as a signal-anchor domain. NIH 3T3 cells transformed by the signal/anchor-sis constructs exhibited morphological reversion upon treatment with suramin, indicating a requirement for ligand/receptor interactions in a suramin- sensitive compartment, most likely the cell surface. In contrast, NIH 3T3 cells transformed by the E5 oncoprotein did not exhibit morphological reversion in response to suramin.

Full Text

The Full Text of this article is available as a PDF (2.9 MB).

Selected References

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

  1. Adams G. A., Rose J. K. Incorporation of a charged amino acid into the membrane-spanning domain blocks cell surface transport but not membrane anchoring of a viral glycoprotein. Mol Cell Biol. 1985 Jun;5(6):1442–1448. doi: 10.1128/mcb.5.6.1442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson D. M., Lyman S. D., Baird A., Wignall J. M., Eisenman J., Rauch C., March C. J., Boswell H. S., Gimpel S. D., Cosman D. Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell. 1990 Oct 5;63(1):235–243. doi: 10.1016/0092-8674(90)90304-w. [DOI] [PubMed] [Google Scholar]
  3. Bold R. J., Donoghue D. J. Biologically active mutants with deletions in the v-mos oncogene assayed with retroviral vectors. Mol Cell Biol. 1985 Nov;5(11):3131–3138. doi: 10.1128/mcb.5.11.3131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brachmann R., Lindquist P. B., Nagashima M., Kohr W., Lipari T., Napier M., Derynck R. Transmembrane TGF-alpha precursors activate EGF/TGF-alpha receptors. Cell. 1989 Feb 24;56(4):691–700. doi: 10.1016/0092-8674(89)90591-6. [DOI] [PubMed] [Google Scholar]
  5. Brown D. J., Hogue B. G., Nayak D. P. Redundancy of signal and anchor functions in the NH2-terminal uncharged region of influenza virus neuraminidase, a class II membrane glycoprotein. J Virol. 1988 Oct;62(10):3824–3831. doi: 10.1128/jvi.62.10.3824-3831.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burkhardt A., Willingham M., Gay C., Jeang K. T., Schlegel R. The E5 oncoprotein of bovine papillomavirus is oriented asymmetrically in Golgi and plasma membranes. Virology. 1989 May;170(1):334–339. doi: 10.1016/0042-6822(89)90391-7. [DOI] [PubMed] [Google Scholar]
  7. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coussens L., Van Beveren C., Smith D., Chen E., Mitchell R. L., Isacke C. M., Verma I. M., Ullrich A. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature. 1986 Mar 20;320(6059):277–280. doi: 10.1038/320277a0. [DOI] [PubMed] [Google Scholar]
  9. Devare S. G., Reddy E. P., Law J. D., Robbins K. C., Aaronson S. A. Nucleotide sequence of the simian sarcoma virus genome: demonstration that its acquired cellular sequences encode the transforming gene product p28sis. Proc Natl Acad Sci U S A. 1983 Feb;80(3):731–735. doi: 10.1073/pnas.80.3.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DiMaio D., Guralski D., Schiller J. T. Translation of open reading frame E5 of bovine papillomavirus is required for its transforming activity. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1797–1801. doi: 10.1073/pnas.83.6.1797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dolci S., Williams D. E., Ernst M. K., Resnick J. L., Brannan C. I., Lock L. F., Lyman S. D., Boswell H. S., Donovan P. J. Requirement for mast cell growth factor for primordial germ cell survival in culture. Nature. 1991 Aug 29;352(6338):809–811. doi: 10.1038/352809a0. [DOI] [PubMed] [Google Scholar]
  12. Fields S., Winter G., Brownlee G. G. Structure of the neuraminidase gene in human influenza virus A/PR/8/34. Nature. 1981 Mar 19;290(5803):213–217. doi: 10.1038/290213a0. [DOI] [PubMed] [Google Scholar]
  13. Fleming T. P., Matsui T., Molloy C. J., Robbins K. C., Aaronson S. A. Autocrine mechanism for v-sis transformation requires cell surface localization of internally activated growth factor receptors. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8063–8067. doi: 10.1073/pnas.86.20.8063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Giese N. A., Robbins K. C., Aaronson S. A. The role of individual cysteine residues in the structure and function of the v-sis gene product. Science. 1987 Jun 5;236(4806):1315–1318. doi: 10.1126/science.3035718. [DOI] [PubMed] [Google Scholar]
  15. Godin I., Deed R., Cooke J., Zsebo K., Dexter M., Wylie C. C. Effects of the steel gene product on mouse primordial germ cells in culture. Nature. 1991 Aug 29;352(6338):807–809. doi: 10.1038/352807a0. [DOI] [PubMed] [Google Scholar]
  16. Goldstein D. J., Finbow M. E., Andresson T., McLean P., Smith K., Bubb V., Schlegel R. Bovine papillomavirus E5 oncoprotein binds to the 16K component of vacuolar H(+)-ATPases. Nature. 1991 Jul 25;352(6333):347–349. doi: 10.1038/352347a0. [DOI] [PubMed] [Google Scholar]
  17. Goldstein D. J., Kulke R., Dimaio D., Schlegel R. A glutamine residue in the membrane-associating domain of the bovine papillomavirus type 1 E5 oncoprotein mediates its binding to a transmembrane component of the vacuolar H(+)-ATPase. J Virol. 1992 Jan;66(1):405–413. doi: 10.1128/jvi.66.1.405-413.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gray A., Dull T. J., Ullrich A. Nucleotide sequence of epidermal growth factor cDNA predicts a 128,000-molecular weight protein precursor. Nature. 1983 Jun 23;303(5919):722–725. doi: 10.1038/303722a0. [DOI] [PubMed] [Google Scholar]
  19. Green M., Loewenstein P. M. Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell. 1988 Dec 23;55(6):1179–1188. doi: 10.1016/0092-8674(88)90262-0. [DOI] [PubMed] [Google Scholar]
  20. Guan J. L., Machamer C. E., Rose J. K. Glycosylation allows cell-surface transport of an anchored secretory protein. Cell. 1985 Sep;42(2):489–496. doi: 10.1016/0092-8674(85)90106-0. [DOI] [PubMed] [Google Scholar]
  21. Hannink M., Donoghue D. J. Autocrine stimulation by the v-sis gene product requires a ligand-receptor interaction at the cell surface. J Cell Biol. 1988 Jul;107(1):287–298. doi: 10.1083/jcb.107.1.287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hannink M., Donoghue D. J. Biosynthesis of the v-sis gene product: signal sequence cleavage, glycosylation, and proteolytic processing. Mol Cell Biol. 1986 Apr;6(4):1343–1348. doi: 10.1128/mcb.6.4.1343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hannink M., Donoghue D. J. Cell surface expression of membrane-anchored v-sis gene products: glycosylation is not required for cell surface transport. J Cell Biol. 1986 Dec;103(6 Pt 1):2311–2322. doi: 10.1083/jcb.103.6.2311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hannink M., Donoghue D. J. Requirement for a signal sequence in biological expression of the v-sis oncogene. Science. 1984 Dec 7;226(4679):1197–1199. doi: 10.1126/science.6095451. [DOI] [PubMed] [Google Scholar]
  25. Hartmann E., Rapoport T. A., Lodish H. F. Predicting the orientation of eukaryotic membrane-spanning proteins. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5786–5790. doi: 10.1073/pnas.86.15.5786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. High S., Flint N., Dobberstein B. Requirements for the membrane insertion of signal-anchor type proteins. J Cell Biol. 1991 Apr;113(1):25–34. doi: 10.1083/jcb.113.1.25. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hoffmann J. W., Steffen D., Gusella J., Tabin C., Bird S., Cowing D., Weinberg R. A. DNA methylation affecting the expression of murine leukemia proviruses. J Virol. 1982 Oct;44(1):144–157. doi: 10.1128/jvi.44.1.144-157.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Horwitz B. H., Burkhardt A. L., Schlegel R., DiMaio D. 44-amino-acid E5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids. Mol Cell Biol. 1988 Oct;8(10):4071–4078. doi: 10.1128/mcb.8.10.4071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Horwitz B. H., Weinstat D. L., DiMaio D. Transforming activity of a 16-amino-acid segment of the bovine papillomavirus E5 protein linked to random sequences of hydrophobic amino acids. J Virol. 1989 Nov;63(11):4515–4519. doi: 10.1128/jvi.63.11.4515-4519.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Huang E., Nocka K., Beier D. R., Chu T. Y., Buck J., Lahm H. W., Wellner D., Leder P., Besmer P. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell. 1990 Oct 5;63(1):225–233. doi: 10.1016/0092-8674(90)90303-v. [DOI] [PubMed] [Google Scholar]
  31. Kawasaki E. S., Ladner M. B., Wang A. M., Van Arsdell J., Warren M. K., Coyne M. Y., Schweickart V. L., Lee M. T., Wilson K. J., Boosman A. Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science. 1985 Oct 18;230(4723):291–296. doi: 10.1126/science.2996129. [DOI] [PubMed] [Google Scholar]
  32. Kazlauskas A., Cooper J. A. Autophosphorylation of the PDGF receptor in the kinase insert region regulates interactions with cell proteins. Cell. 1989 Sep 22;58(6):1121–1133. doi: 10.1016/0092-8674(89)90510-2. [DOI] [PubMed] [Google Scholar]
  33. Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. doi: 10.1016/0092-8674(86)90762-2. [DOI] [PubMed] [Google Scholar]
  34. Kundu A., Jabbar M. A., Nayak D. P. Cell surface transport, oligomerization, and endocytosis of chimeric type II glycoproteins: role of cytoplasmic and anchor domains. Mol Cell Biol. 1991 May;11(5):2675–2685. doi: 10.1128/mcb.11.5.2675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. LaRochelle W. J., Giese N., May-Siroff M., Robbins K. C., Aaronson S. A. Molecular localization of the transforming and secretory properties of PDGF A and PDGF B. Science. 1990 Jun 22;248(4962):1541–1544. doi: 10.1126/science.2163109. [DOI] [PubMed] [Google Scholar]
  36. LaRochelle W. J., May-Siroff M., Robbins K. C., Aaronson S. A. A novel mechanism regulating growth factor association with the cell surface: identification of a PDGF retention domain. Genes Dev. 1991 Jul;5(7):1191–1199. doi: 10.1101/gad.5.7.1191. [DOI] [PubMed] [Google Scholar]
  37. LaRochelle W. J., Robbins K. C., Aaronson S. A. Immunochemical localization of the epitope for a monoclonal antibody that neutralizes human platelet-derived growth factor mitogenic activity. Mol Cell Biol. 1989 Aug;9(8):3538–3542. doi: 10.1128/mcb.9.8.3538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lee B. A., Donoghue D. J. Membrane-anchored form of v-sis/PDGF-B induces mitogenesis without detectable PDGF receptor autophosphorylation. J Cell Biol. 1991 Apr;113(2):361–370. doi: 10.1083/jcb.113.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lipp J., Dobberstein B. Signal and membrane anchor functions overlap in the type II membrane protein I gamma CAT. J Cell Biol. 1988 Jun;106(6):1813–1820. doi: 10.1083/jcb.106.6.1813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lokeshwar V. B., Huang S. S., Huang J. S. Intracellular turnover, novel secretion, and mitogenically active intracellular forms of v-sis gene product in simian sarcoma virus-transformed cells. Implications for intracellular loop autocrine transformation. J Biol Chem. 1990 Jan 25;265(3):1665–1675. [PubMed] [Google Scholar]
  41. Matsui T., Heidaran M., Miki T., Popescu N., La Rochelle W., Kraus M., Pierce J., Aaronson S. Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes. Science. 1989 Feb 10;243(4892):800–804. doi: 10.1126/science.2536956. [DOI] [PubMed] [Google Scholar]
  42. Melton D. A. Translation of messenger RNA in injected frog oocytes. Methods Enzymol. 1987;152:288–296. doi: 10.1016/0076-6879(87)52033-x. [DOI] [PubMed] [Google Scholar]
  43. Nayak D. P., Jabbar M. A. Structural domains and organizational conformation involved in the sorting and transport of influenza virus transmembrane proteins. Annu Rev Microbiol. 1989;43:465–501. doi: 10.1146/annurev.mi.43.100189.002341. [DOI] [PubMed] [Google Scholar]
  44. Petti L., DiMaio D. Stable association between the bovine papillomavirus E5 transforming protein and activated platelet-derived growth factor receptor in transformed mouse cells. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6736–6740. doi: 10.1073/pnas.89.15.6736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Petti L., Nilson L. A., DiMaio D. Activation of the platelet-derived growth factor receptor by the bovine papillomavirus E5 transforming protein. EMBO J. 1991 Apr;10(4):845–855. doi: 10.1002/j.1460-2075.1991.tb08017.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Qiu F. H., Ray P., Brown K., Barker P. E., Jhanwar S., Ruddle F. H., Besmer P. Primary structure of c-kit: relationship with the CSF-1/PDGF receptor kinase family--oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. EMBO J. 1988 Apr;7(4):1003–1011. doi: 10.1002/j.1460-2075.1988.tb02907.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Raines E. W., Ross R. Compartmentalization of PDGF on extracellular binding sites dependent on exon-6-encoded sequences. J Cell Biol. 1992 Jan;116(2):533–543. doi: 10.1083/jcb.116.2.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Rawls J. A., Loewenstein P. M., Green M. Mutational analysis of bovine papillomavirus type 1 E5 peptide domains involved in induction of cellular DNA synthesis. J Virol. 1989 Nov;63(11):4962–4964. doi: 10.1128/jvi.63.11.4962-4964.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Rettenmier C. W., Roussel M. F. Differential processing of colony-stimulating factor 1 precursors encoded by two human cDNAs. Mol Cell Biol. 1988 Nov;8(11):5026–5034. doi: 10.1128/mcb.8.11.5026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Robbins K. C., Leal F., Pierce J. H., Aaronson S. A. The v-sis/PDGF-2 transforming gene product localizes to cell membranes but is not a secretory protein. EMBO J. 1985 Jul;4(7):1783–1792. doi: 10.1002/j.1460-2075.1985.tb03851.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Rose J. K., Gallione C. J. Nucleotide sequences of the mRNA's encoding the vesicular stomatitis virus G and M proteins determined from cDNA clones containing the complete coding regions. J Virol. 1981 Aug;39(2):519–528. doi: 10.1128/jvi.39.2.519-528.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sauer M. K., Donoghue D. J. Identification of nonessential disulfide bonds and altered conformations in the v-sis protein, a homolog of the B chain of platelet-derived growth factor. Mol Cell Biol. 1988 Mar;8(3):1011–1018. doi: 10.1128/mcb.8.3.1011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Schlegel R., Wade-Glass M., Rabson M. S., Yang Y. C. The E5 transforming gene of bovine papillomavirus encodes a small, hydrophobic polypeptide. Science. 1986 Jul 25;233(4762):464–467. doi: 10.1126/science.3014660. [DOI] [PubMed] [Google Scholar]
  54. Schneider C., Owen M. J., Banville D., Williams J. G. Primary structure of human transferrin receptor deduced from the mRNA sequence. Nature. 1984 Oct 18;311(5987):675–678. doi: 10.1038/311675b0. [DOI] [PubMed] [Google Scholar]
  55. Scott J., Selby M., Urdea M., Quiroga M., Bell G. I., Rutter W. J. Isolation and nucleotide sequence of a cDNA encoding the precursor of mouse nerve growth factor. Nature. 1983 Apr 7;302(5908):538–540. doi: 10.1038/302538a0. [DOI] [PubMed] [Google Scholar]
  56. Shibuya M., Yamaguchi S., Yamane A., Ikeda T., Tojo A., Matsushime H., Sato M. Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene. 1990 Apr;5(4):519–524. [PubMed] [Google Scholar]
  57. Sivasubramanian N., Nayak D. P. Mutational analysis of the signal-anchor domain of influenza virus neuraminidase. Proc Natl Acad Sci U S A. 1987 Jan;84(1):1–5. doi: 10.1073/pnas.84.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Spiess M., Lodish H. F. An internal signal sequence: the asialoglycoprotein receptor membrane anchor. Cell. 1986 Jan 17;44(1):177–185. doi: 10.1016/0092-8674(86)90496-4. [DOI] [PubMed] [Google Scholar]
  59. Spiess M., Lodish H. F. Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6465–6469. doi: 10.1073/pnas.82.19.6465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Spiess M., Schwartz A. L., Lodish H. F. Sequence of human asialoglycoprotein receptor cDNA. An internal signal sequence for membrane insertion. J Biol Chem. 1985 Feb 25;260(4):1979–1982. [PubMed] [Google Scholar]
  61. Stroobant P., Rice A. P., Gullick W. J., Cheng D. J., Kerr I. M., Waterfield M. D. Purification and characterization of vaccinia virus growth factor. Cell. 1985 Aug;42(1):383–393. doi: 10.1016/s0092-8674(85)80133-1. [DOI] [PubMed] [Google Scholar]
  62. Walter P., Lingappa V. R. Mechanism of protein translocation across the endoplasmic reticulum membrane. Annu Rev Cell Biol. 1986;2:499–516. doi: 10.1146/annurev.cb.02.110186.002435. [DOI] [PubMed] [Google Scholar]
  63. Wong G. G., Temple P. A., Leary A. C., Witek-Giannotti J. S., Yang Y. C., Ciarletta A. B., Chung M., Murtha P., Kriz R., Kaufman R. J. Human CSF-1: molecular cloning and expression of 4-kb cDNA encoding the human urinary protein. Science. 1987 Mar 20;235(4795):1504–1508. doi: 10.1126/science.3493529. [DOI] [PubMed] [Google Scholar]
  64. Wong S. T., Winchell L. F., McCune B. K., Earp H. S., Teixidó J., Massagué J., Herman B., Lee D. C. The TGF-alpha precursor expressed on the cell surface binds to the EGF receptor on adjacent cells, leading to signal transduction. Cell. 1989 Feb 10;56(3):495–506. doi: 10.1016/0092-8674(89)90252-3. [DOI] [PubMed] [Google Scholar]
  65. Yarden Y., Escobedo J. A., Kuang W. J., Yang-Feng T. L., Daniel T. O., Tremble P. M., Chen E. Y., Ando M. E., Harkins R. N., Francke U. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors. Nature. 1986 Sep 18;323(6085):226–232. doi: 10.1038/323226a0. [DOI] [PubMed] [Google Scholar]
  66. Zerial M., Melancon P., Schneider C., Garoff H. The transmembrane segment of the human transferrin receptor functions as a signal peptide. EMBO J. 1986 Jul;5(7):1543–1550. doi: 10.1002/j.1460-2075.1986.tb04395.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. de Vries C., Escobedo J. A., Ueno H., Houck K., Ferrara N., Williams L. T. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science. 1992 Feb 21;255(5047):989–991. doi: 10.1126/science.1312256. [DOI] [PubMed] [Google Scholar]

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

RESOURCES