gag onc fusion proteins


Summary: General name for the translation products of a fusion mRNA consisting of a gag gene and a viral oncogene (v-onc). These products are thought to have the ability to transform cells.

Top Publications

  1. Kamata N, Jotte R, Holt J. Myristylation alters DNA-binding activity and transactivation of FBR (gag-fos) protein. Mol Cell Biol. 1991;11:765-72 pubmed
    ..These findings demonstrate that protein myristylation can modulate gene regulation by a DNA-binding protein...
  2. Lin C, Maher V, McCormick J. Malignant transformation of human fibroblast strain MSU-1.1 by v-fes requires an additional genetic change. Int J Cancer. 1995;63:140-7 pubmed
    ..The results showed that when complemented either by a ras oncogene expressed at a somewhat enhanced level or by the v-sis oncogene, v-fes can supply the additional change required for malignant transformation. ..
  3. Smithgall T, Rogers J, Peters K, Li J, Briggs S, Lionberger J, et al. The c-Fes family of protein-tyrosine kinases. Crit Rev Oncog. 1998;9:43-62 pubmed
    ..This review highlights the unique aspects of Fes structure, regulation, and function that set it apart from other tyrosine kinase families. ..
  4. Craig A, Zirngibl R, Greer P. Disruption of coiled-coil domains in Fer protein-tyrosine kinase abolishes trimerization but not kinase activation. J Biol Chem. 1999;274:19934-42 pubmed
    ..These results suggest that although oligomerization potentiates autophosphorylation in trans, this is apparently not necessary for Fer activation. ..
  5. Kirito K, Nakajima K, Watanabe T, Uchida M, Tanaka M, Ozawa K, et al. Identification of the human erythropoietin receptor region required for Stat1 and Stat3 activation. Blood. 2002;99:102-10 pubmed
    ..In addition, Jak2 and Fes tyrosine kinases were involved in EPO-induced activation of Stat1 and Stat3. These results indicate that Stat1 and Stat3 are activated by EPO via distinct mechanisms from Stat5. ..
  6. Alexandropoulos K, Qureshi S, Bruder J, Rapp U, Foster D. The induction of Egr-1 expression by v-Fps is via a protein kinase C-independent intracellular signal that is sequentially dependent upon HaRas and Raf-1. Cell Growth Differ. 1992;3:731-7 pubmed
    ..These data suggest that v-Fps activates a protein kinase C-independent intracellular signaling pathway that is dependent on both HaRas and Raf-1, where Raf-1 functions downstream of HaRas. ..
  7. Ellis C, Moran M, McCormick F, Pawson T. Phosphorylation of GAP and GAP-associated proteins by transforming and mitogenic tyrosine kinases. Nature. 1990;343:377-81 pubmed
    ..These data support the idea that SH2 sequences direct the interactions of cytoplasmic proteins involved in signal transduction. ..
  8. Hjermstad S, Peters K, Briggs S, Glazer R, Smithgall T. Regulation of the human c-fes protein tyrosine kinase (p93c-fes) by its src homology 2 domain and major autophosphorylation site (Tyr-713). Oncogene. 1993;8:2283-92 pubmed
    ..These results indicate that the c-fes SH2 domain and consensus autophosphorylation site (Tyr-713) play major roles in the positive regulation of p93c-fes tyrosine kinase activity, possibly through intramolecular interaction. ..
  9. Alexandropoulos K, Qureshi S, Foster D. Ha-Ras functions downstream from protein kinase C in v-Fps-induced gene expression mediated by TPA response elements. Oncogene. 1993;8:803-7 pubmed
    ..Thus, v-Fps-induced activation of TRE-mediated gene expression is via an intracellular signaling mechanism that is dependent upon both PKC and Ha-Ras and Ha-Ras functions downstream from PKC. ..

More Information


  1. Saylor P, Wang C, Hirai T, Adams J. A second magnesium ion is critical for ATP binding in the kinase domain of the oncoprotein v-Fps. Biochemistry. 1998;37:12624-30 pubmed
    ..While the second metal could have some influence on phosphoryl transfer or product binding, it is a potent activator that functions minimally by controlling ATP-Mg binding. ..
  2. Rogers J, Cheng H, Smithgall T. Src homology 2 domain substitution modulates the kinase and transforming activities of the Fes protein-tyrosine kinase. Cell Growth Differ. 2000;11:581-92 pubmed
    ..These data demonstrate a central role for the SH2 domain in the regulation of Fes kinase activity and biological function in vivo. ..
  3. Law W, Linial M. Transforming ability of Gag-Myc fusion proteins correlates with Gag-Myc protein stability and transcriptional repression. Oncogene. 2001;20:1118-27 pubmed
    ..Taken together, these results suggest that protein stabilization of Myc and repression of target genes by Myc are important for cellular transformation. ..
  4. Greer P. Closing in on the biological functions of Fps/Fes and Fer. Nat Rev Mol Cell Biol. 2002;3:278-89 pubmed
    ..Genetic analysis using transgenic mouse models also implicates these kinases in the regulation of inflammation and innate immunity. ..
  5. Rovida E, Marra F, Baccarini M, Dello Sbarba P. Constitutive activation of the MAPK pathway mediates v-fes-induced mitogenesis in murine macrophages. Blood. 2000;95:3959-63 pubmed
    ..Blood. 2000;95:3959-3963) ..
  6. Meckling Gill K, Cass C. Effects of transformation by v-fps on nucleoside transport in Rat-2 fibroblasts. Biochem J. 1992;282 ( Pt 1):147-54 pubmed
    ..Thus transformation by v-fps resulted in an increase in NBMPR-sensitive transport activity which was not related to either the number of NBMPR-binding sites or the apparent molecular mass of NBMPR-binding polypeptides. ..
  7. Saylor P, Hanna E, Adams J. Mutations in the activation loop tyrosine of the oncoprotein v-Fps. Biochemistry. 1998;37:17875-81 pubmed
    ..1995) Biochemistry 34, 2447-2454] upon autophosphorylation suggest a conserved mechanism for communication between the activation loop and the catalytic residues of these two enzymes. ..
  8. Kim J, Ogata Y, Ali H, Feldman R. The Fes tyrosine kinase: a signal transducer that regulates myeloid-specific gene expression through transcriptional activation. Blood Cells Mol Dis. 2004;32:302-8 pubmed
    ..We postulate that Fes transduces inductive signals for terminal macrophage and granulocyte differentiation, and that this biological activity is mediated through the activation of lineage-specific transcription factors. ..
  9. Bai W, Singh B, Karshin W, Shonk R, Arlinghaus R. Phosphorylation of v-mos Ser 47 by the mitotic form of p34cdc2. Oncogene. 1991;6:1715-23 pubmed
    ..These results were unexpected in view of earlier reports regarding cdc2 kinase activation/stabilization by the c-mos kinase in maturing oocytes. ..
  10. Fan H, Villegas C, Huang A, Wright J. The mammalian ribonucleotide reductase R2 component cooperates with a variety of oncogenes in mechanisms of cellular transformation. Cancer Res. 1998;58:1650-3 pubmed
  11. Giambernardi T, Grant G, Taylor G, Hay R, Maher V, McCormick J, et al. Overview of matrix metalloproteinase expression in cultured human cells. Matrix Biol. 1998;16:483-96 pubmed
    ..Identification of at least one cell line expressing each of thirteen MMPs and the observation of oncogene induced expression of several MMPs should facilitate analysis of the transcriptional mechanisms controlling each MMP. ..
  12. Zirngibl R, Schulze D, Mirski S, Cole S, Greer P. Subcellular localization analysis of the closely related Fps/Fes and Fer protein-tyrosine kinases suggests a distinct role for Fps/Fes in vesicular trafficking. Exp Cell Res. 2001;266:87-94 pubmed
    ..These results suggest that Fps/Fes may play a general role in the regulation of vesicular trafficking. ..
  13. Liebl E, England L, Martin G. Reactivation of host-dependent src kinase activity by co-expression with a heterologous tyrosine kinase. Virology. 1993;195:265-7 pubmed
    ..The reactivation of XD4-src may result either from direct phosphorylation by the v-fps gene product or may be an indirect consequence of v-fps expression. ..
  14. Adams J. Insight into tyrosine phosphorylation in v-Fps using proton inventory techniques. Biochemistry. 1996;35:10949-56 pubmed
    ..The combined data are consistent with a mechanism involving either an acid-base catalyst or a conformational change preceding the release of products that is accompanied by the disruption of a single hydrogen donor-acceptor pair. ..
  15. Alexandropoulos K, Joseph C, Spangler R, Foster D. Evidence that a G-protein transduces signals initiated by the protein-tyrosine kinase v-Fps. J Biol Chem. 1991;266:15583-6 pubmed
    ..The data suggest that a G-protein functions upstream from PKC in a signaling pathway that connects v-Fps PTK activity to increased 9E3 gene expression. ..
  16. Maru Y, Peters K, Afar D, Shibuya M, Witte O, Smithgall T. Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS. Mol Cell Biol. 1995;15:835-42 pubmed
    ..These data provide evidence that BCR couples the cytoplasmic protein-tyrosine kinase and RAS signaling pathways. ..
  17. Taniguchi S, Tatsuka M, Nakamatsu K, Inoue M, Sadano H, Okazaki H, et al. High invasiveness associated with augmentation of motility in a fos-transferred highly metastatic rat 3Y1 cell line. Cancer Res. 1989;49:6738-44 pubmed
    ..Thus, the fos-transferred cell line, fos-SR-3Y1-202 has a high invasiveness, in association with augmentation of motility, hence the enhancement of metastatic potential. ..
  18. Bardelli A, Parsons D, Silliman N, Ptak J, Szabo S, Saha S, et al. Mutational analysis of the tyrosine kinome in colorectal cancers. Science. 2003;300:949 pubmed
  19. Jiang Y, Song J, Zang Q, Foster D. Phosphatidylcholine-specific phospholipase D activity is elevated in v-Fps-transformed cells. Biochem Biophys Res Commun. 1994;203:1195-2003 pubmed
    ..The increased PLD activity was detected only when the cells were prelabeled with the PC-specific [3H]-myristate. These data support the hypothesis that v-Fps-induced DG is derived from PC via the PLD/PAP pathway. ..
  20. Martin A, Gomez Munoz A, Waggoner D, Stone J, Brindley D. Decreased activities of phosphatidate phosphohydrolase and phospholipase D in ras and tyrosine kinase (fps) transformed fibroblasts. J Biol Chem. 1993;268:23924-32 pubmed
    ..Control of PAP-2 activity could be an important factor in regulating appropriate signals for cell division. ..
  21. Kamata N, Holt J. Inhibitory effect of myristylation on transrepression by FBR (Gag-Fos) protein. Mol Cell Biol. 1992;12:876-82 pubmed
  22. Anderson D, Ismail P. v-fps causes transformation by inducing tyrosine phosphorylation and activation of the PDGFbeta receptor. Oncogene. 1998;16:2321-31 pubmed
  23. Alexandropoulos K, Qureshi S, Rim M, Sukhatme V, Foster D. v-Fps-responsiveness in the Egr-1 promoter is mediated by serum response elements. Nucleic Acids Res. 1992;20:2355-9 pubmed
    ..These data suggest that v-Fps-responsiveness in the Egr-1 promoter is mediated by SREs. ..
  24. Jähner D, Hunter T. The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts. Mol Cell Biol. 1991;11:3682-90 pubmed
    ..Neither the closely related rhoC and rhoA genes nor the distantly related c-H-ras gene is rapidly inducible by mitogens. Thus, rhoB is the first known member of the small GTP-binding proteins among the immediate-early genes. ..
  25. Yuen P, Devroe E, Lim K, Wong P. Changes in the N- and C-terminal sequences of the murine R7 Gag-tMos protein affect brain lesion induction. J Neurovirol. 2000;6:329-40 pubmed
    ..Thus, we have demonstrated that altering the N- or C-terminus of the R7 Gag-tMos fusion protein can affect disease manifestation. ..
  26. Jong S, Wang L. Role of gag sequence in the biochemical properties and transforming activity of the avian sarcoma virus UR2-encoded gag-ros fusion protein. J Virol. 1990;64:5997-6009 pubmed
    ..We conclude that the gag sequence is essential for the transforming activity of P68gag-ros but is not important for its membrane association. ..
  27. Pinilla C, Appel J, Houghten R. Functional importance of amino acid residues making up peptide antigenic determinants. Mol Immunol. 1993;30:577-85 pubmed
    ..It is of interest that the positional arrangement of specific and nonspecific residues were different for each of the three antigenic determinants examined. ..
  28. Ogiso Y, Yokoyama T, Watari H, Shih T, Kuzumaki N. Resistance of NIH3T3 cells to v-fes transformation induced by a dominant negative H-ras mutant. Exp Cell Res. 1993;208:415-21 pubmed
    ..Inhibition of the ras function may down-regulate this pathway and result in resistance to transformation by v-fes. ..
  29. Kopelovich L. Conversion of human fibroblasts to tissue macrophages by the Snyder-Theilen sarcoma virus (ST:FeSV): tumouricidal effects on K-562 and Daudi tumour cell lines in monolayers and in agar suspensions. Eur Cytokine Netw. 1993;4:263-8 pubmed
    ..The results indicate that ST:FeSV-induced TM are potent oncocytotoxic agents of K-562 tumour cells, but are considerably less effective against the Daudi tumour cells...
  30. Meijne A, Ruuls Van Stalle L, Feltkamp C, McCarthy J, Roos E. v-src-induced cell shape changes in rat fibroblasts require new gene transcription and precede loss of focal adhesions. Exp Cell Res. 1997;234:477-85 pubmed
    ..We conclude that v-src-induced transformation of rat fibroblasts depends on synthesis of a protein, which induces rapid changes in cell shape that precede the loss of focal adhesions. ..
  31. Jong S, Wang L. Two point mutations in the transmembrane domain of P68gag-ros inactive its transforming activity and cause a delay in membrane association. J Virol. 1991;65:180-9 pubmed
    ..Changes of P68TM in the kinetics of membrane association indicate that the transmembrane domain of ros, besides functioning as a membrane anchor, also plays a role in directing initial membrane association. ..
  32. Hirai T, Tsigelny I, Adams J. Catalytic assessment of the glycine-rich loop of the v-Fps oncoprotein using site-directed mutagenesis. Biochemistry. 2000;39:13276-84 pubmed
    ..These effects on nucleotide specificity may be a contributing element for the stabilization of the phosphoryl transition state and may also facilitate quick release of bound products. ..
  33. Jähner D, Hunter T. The stimulation of quiescent rat fibroblasts by v-src and v-fps oncogenic protein-tyrosine kinases leads to the induction of a subset of immediate early genes. Oncogene. 1991;6:1259-68 pubmed
    ..Furthermore, we demonstrated that the induction of several of these genes by the retroviral oncogenic protein-tyrosine kinases is rapid, direct and occurs at the transcriptional level. ..
  34. Wang C, Lee T, Lawrence D, Adams J. Rate-determining steps for tyrosine phosphorylation by the kinase domain of v-fps. Biochemistry. 1996;35:1533-9 pubmed
    ..This implies that the differences in catalytic efficiency between serine- and tyrosine-specific protein kinases lie exclusively in the rate constants for phosphoryl group transfer and not in substrate absorption or product desorption. ..
  35. Moran M, Koch C, Sadowski I, Pawson T. Mutational analysis of a phosphotransfer motif essential for v-fps tyrosine kinase activity. Oncogene. 1988;3:665-72 pubmed
  36. Chow L, Yee S, Pawson T, McManus B. Progressive cardiac fibrosis and myocyte injury in v-fps transgenic mice. A model for primary disorders of connective tissue in the heart?. Lab Invest. 1991;64:457-62 pubmed
    ..Collectively, the data suggest a primary proliferative abnormality of connective tissue elements in the heart, accompanied by secondary myocyte damage. ..
  37. Letwin K, Yee S, Pawson T. Novel protein-tyrosine kinase cDNAs related to fps/fes and eph cloned using anti-phosphotyrosine antibody. Oncogene. 1988;3:621-7 pubmed
    ..The preferential isolation of cDNAs for previously uncharacterized protein-tyrosine kinases in a screen based on catalytic activity suggests that additional members of the protein-tyrosine kinase family remain to be identified. ..
  38. Haigh J, Ema M, Haigh K, Gertsenstein M, Greer P, Rossant J, et al. Activated Fps/Fes partially rescues the in vivo developmental potential of Flk1-deficient vascular progenitor cells. Blood. 2004;103:912-20 pubmed
    ..We have also demonstrated that activated Fps/Fes causes hemangioma formation in vivo, independently of Flk1, as a result of increasing vascular progenitor density. ..
  39. Meckling Gill K, Yee S, Schrader J, Pawson T. A retrovirus encoding the v-fps protein-tyrosine kinase induces factor-independent growth and tumorigenicity in FDC-P1 cells. Biochim Biophys Acta. 1992;1137:65-72 pubmed
    ..We suggest that P130gag-fps is acting to directly stimulate a hematopoietic growth-factor signalling pathway, perhaps one that normally involves the endogenous c-fps/fes protein-tyrosine kinase of FDC-P1 cells. ..
  40. Leon B, Tsigelny I, Adams J. Electrostatic environment surrounding the activation loop phosphotyrosine in the oncoprotein v-Fps. Biochemistry. 2001;40:10078-86 pubmed
    ..While this strain is not relieved in the phosphorylated form, the improvements in catalysis in activated v-Fps compensate for reduced metal and substrate binding affinities. ..
  41. Sangrar W, Gao Y, Bates B, Zirngibl R, Greer P. Activated Fps/Fes tyrosine kinase regulates erythroid differentiation and survival. Exp Hematol. 2004;32:935-45 pubmed
    ..The anemic phenotype in fps(MF) mice suggests that downregulation of Fps/Fes activity might be required for terminal erythroid differentiation. ..
  42. Kim J, Feldman R. Activated Fes protein tyrosine kinase induces terminal macrophage differentiation of myeloid progenitors (U937 cells) and activation of the transcription factor PU.1. Mol Cell Biol. 2002;22:1903-18 pubmed
    ..Our results strongly implicate Fes as a key regulator of terminal macrophage differentiation and identify PU.1 as a transcription factor that may mediate some of its biological activities in myeloid cells. ..
  43. Sangrar W, Gao Y, Zirngibl R, Scott M, Greer P. The fps/fes proto-oncogene regulates hematopoietic lineage output. Exp Hematol. 2003;31:1259-67 pubmed
    ..These observations support a role for Fps/Fes in signaling pathways that contribute to lineage determination at the level of multi-lineage hematopoietic progenitors as well as the more committed granulomonocytic progenitors. ..
  44. Senis Y, Craig A, Greer P. Fps/Fes and Fer protein-tyrosinekinases play redundant roles in regulating hematopoiesis. Exp Hematol. 2003;31:673-81 pubmed
    ..Mice lacking both Fps and Fer kinase activities develop normally, show reduced fertility, and display defects in hematopoiesis, thus providing evidence for functional redundancy between Fps and Fer kinases in regulating hematopoiesis. ..
  45. Takahashi S, Inatome R, Hotta A, Qin Q, Hackenmiller R, Simon M, et al. Role for Fes/Fps tyrosine kinase in microtubule nucleation through is Fes/CIP4 homology domain. J Biol Chem. 2003;278:49129-33 pubmed
    ..Our findings suggest that Fes plays a critical role in microtubule dynamics including microtubule nucleation and bundling through its FCH domain. ..
  46. Boulton T, Gregory J, Jong S, Wang L, Ellis L, Cobb M. Evidence for insulin-dependent activation of S6 and microtubule-associated protein-2 kinases via a human insulin receptor/v-ros hybrid. J Biol Chem. 1990;265:2713-9 pubmed
    ..L. (1988) Nature 334, 715-718). We find that the IRros receptor stimulates the MAP2 protein kinase from 3- to 6-fold in insulin-treated cells, conferring more than a 30-fold increase in the insulin sensitivity of MAP2 kinase activation. ..
  47. Peters E, Wilderspin A, Wood S, Zvelebil M, Sezer O, Danchin A. A pyruvate-stimulated adenylate cyclase has a sequence related to the fes/fps oncogenes and to eukaryotic cyclases. Mol Microbiol. 1991;5:1175-81 pubmed
  48. Konkol L, Hirai T, Adams J. Substrate specificity of the oncoprotein v-Fps: site-specific mutagenesis of the putative P+1 pocket. Biochemistry. 2000;39:255-62 pubmed
  49. Martin A, Duffy P, Liossis C, Gomez Munoz A, O BRIEN L, Stone J, et al. Increased concentrations of phosphatidate, diacylglycerol and ceramide in ras- and tyrosine kinase (fps)-transformed fibroblasts. Oncogene. 1997;14:1571-80 pubmed
    ..The consequences of increased ceramide and phosphatidate concentrations in ras-transformed cells are discussed in relation to signal transduction, cell division and the transformed phenotype. ..
  50. Koch C, Moran M, Sadowski I, Pawson T. The common src homology region 2 domain of cytoplasmic signaling proteins is a positive effector of v-fps tyrosine kinase function. Mol Cell Biol. 1989;9:4131-40 pubmed
    ..The SH2 domain therefore appears to play a dual role in regulation of kinase activity and recognition of cellular substrates. ..
  51. Appleby M, Greenfield I, Crook T, Parkinson E, Stanley M. In vivo and in vitro effects of v-fos and EJ-Ha-ras oncogene expression in murine epidermal keratinocytes. Oncogene. 1989;4:1323-30 pubmed
    ..14 cm2 is required before a full thickness epithelium forms. ..
  52. Maruyama K, Fukushima T, Miyauchi M, Koshikawa N, Kawamura K, Mochizuki S. V-onc mutation associated with host cell growth in retroviral tumors. Leukemia. 1995;9 Suppl 1:S89-92 pubmed
  53. Mano H, Mano K, Tang B, Koehler M, Yi T, Gilbert D, et al. Expression of a novel form of Tec kinase in hematopoietic cells and mapping of the gene to chromosome 5 near Kit. Oncogene. 1993;8:417-24 pubmed
    ..Lastly, by interspecies backcross analysis, we show that the Tec gene is tightly linked to the c-Kit gene on mouse chromosome 5. ..