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Gene Review

Tgfa  -  transforming growth factor alpha

Mus musculus

Synonyms: Protransforming growth factor alpha, wa-1, wa1
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Disease relevance of Tgfa


Psychiatry related information on Tgfa

  • Female mice coexpressing TGF-alpha and neu developed multifocal mammary tumors which arose after a significantly shorter latency period than either parental strain alone [4].
  • To study the role of EGF, TGF-alpha and EGFR in early human development, two methods applicable for analysis of expression at the single embryo level have been employed [6].
  • TGF-alpha is expressed rhythmically in the SCN, and when infused into the third ventricle it reversibly inhibited locomotor activity and disrupted circadian sleep-wake cycles [7].

High impact information on Tgfa


Chemical compound and disease context of Tgfa


Biological context of Tgfa


Anatomical context of Tgfa


Associations of Tgfa with chemical compounds

  • Mice heterozygous for the N-ethyl-N-nitrosourea-induced Waved-5 (Wa5) mutation, isolated in a screen for dominant, visible mutations, exhibit a wavy coat similar to mice homozygous for the recessive Tgfa wa1 or Egfr wa2 alleles [22].
  • Pharmacologic inhibition of AngII prevented TGF-alpha and TACE accumulation as well as renal lesions after nephron reduction [19].
  • We found that EGF continues to stimulate maximal tyrosine phosphorylation of EGFR following internalization, while, as expected, TGFalpha stimulates markedly less [23].
  • The half-life of TGF-alpha mRNA is 40-60 min in antisense cells and more than 8 h in parental KB cells, as determined by actinomycin D decay curves [24].
  • The resulting higher level of receptor activation by EGF, however, did not yield higher levels of phosphatidylinositol (4,5)-bisphosphate (PIP2) hydrolysis over those stimulated by TGFalpha [23].

Physical interactions of Tgfa


Enzymatic interactions of Tgfa

  • The PKCdelta that was tyrosine-phosphorylated in response to TGFalpha had reduced activity compared with the nontyrosine-phosphorylated PKCdelta [30].
  • The neurotrophic actions of HB-EGF and TGFalpha are accompanied by an elevation in immunoreactive dual phosphorylated mitogen-activated protein kinase (MAP kinase) in neurons, providing evidence that the MAP kinase cascade mediates these actions [31].

Regulatory relationships of Tgfa


Other interactions of Tgfa


Analytical, diagnostic and therapeutic context of Tgfa


  1. Epidermal growth factor receptor occupancy inhibits vaccinia virus infection. Eppstein, D.A., Marsh, Y.V., Schreiber, A.B., Newman, S.R., Todaro, G.J., Nestor, J.J. Nature (1985) [Pubmed]
  2. Transgenic mice provide new insights into the role of TGF-alpha during epidermal development and differentiation. Vassar, R., Fuchs, E. Genes Dev. (1991) [Pubmed]
  3. Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas. Vinter-Jensen, L., Juhl, C.O., Teglbjaerg, P.S., Poulsen, S.S., Dajani, E.Z., Nexø, E. Gastroenterology (1997) [Pubmed]
  4. Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice. Muller, W.J., Arteaga, C.L., Muthuswamy, S.K., Siegel, P.M., Webster, M.A., Cardiff, R.D., Meise, K.S., Li, F., Halter, S.A., Coffey, R.J. Mol. Cell. Biol. (1996) [Pubmed]
  5. Autonomous growth in serum-free medium and production of hepatocellular carcinomas by differentiated hepatocyte lines that overexpress transforming growth factor alpha 1. Wu, J.C., Merlino, G., Cveklova, K., Mosinger, B., Fausto, N. Cancer Res. (1994) [Pubmed]
  6. EGF, TGF-alpha and EGFR expression in human preimplantation embryos. Chia, C.M., Winston, R.M., Handyside, A.H. Development (1995) [Pubmed]
  7. Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling. Kramer, A., Yang, F.C., Snodgrass, P., Li, X., Scammell, T.E., Davis, F.C., Weitz, C.J. Science (2001) [Pubmed]
  8. Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha. Garrett, T.P., McKern, N.M., Lou, M., Elleman, T.C., Adams, T.E., Lovrecz, G.O., Zhu, H.J., Walker, F., Frenkel, M.J., Hoyne, P.A., Jorissen, R.N., Nice, E.C., Burgess, A.W., Ward, C.W. Cell (2002) [Pubmed]
  9. Mice with a null mutation of the TGF alpha gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation. Mann, G.B., Fowler, K.J., Gabriel, A., Nice, E.C., Williams, R.L., Dunn, A.R. Cell (1993) [Pubmed]
  10. TGF alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Luetteke, N.C., Qiu, T.H., Peiffer, R.L., Oliver, P., Smithies, O., Lee, D.C. Cell (1993) [Pubmed]
  11. Transforming growth factor-alpha deficiency reduces pulmonary fibrosis in transgenic mice. Madtes, D.K., Elston, A.L., Hackman, R.C., Dunn, A.R., Clark, J.G. Am. J. Respir. Cell Mol. Biol. (1999) [Pubmed]
  12. Biological activity of a transforming growth factor-alpha--Pseudomonas exotoxin fusion protein in vitro and in vivo. Heimbrook, D.C., Stirdivant, S.M., Ahern, J.D., Balishin, N.L., Patrick, D.R., Edwards, G.M., Defeo-Jones, D., FitzGerald, D.J., Pastan, I., Oliff, A. J. Ind. Microbiol. (1991) [Pubmed]
  13. Teratogenic effects of retinoic acid are modulated in mice lacking expression of epidermal growth factor and transforming growth factor-alpha. Abbott, B.D., Best, D.S., Narotsky, M.G. Birth defects research. Part A, Clinical and molecular teratology. (2005) [Pubmed]
  14. Abrogation of transforming growth factor-alpha/epidermal growth factor receptor autocrine signaling by an RXR-selective retinoid (LGD1069, Targretin) in head and neck cancer cell lines. Song, J.I., Lango, M.N., Hwang, J.D., Drenning, S.D., Zeng, Q., Lamph, W.W., Grandis, J.R. Cancer Res. (2001) [Pubmed]
  15. Phenobarbital promotes liver growth in c-myc/TGF-alpha transgenic mice by inducing hypertrophy and inhibiting apoptosis. Sanders, S., Thorgeirsson, S.S. Carcinogenesis (1999) [Pubmed]
  16. Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Miettinen, P.J., Berger, J.E., Meneses, J., Phung, Y., Pedersen, R.A., Werb, Z., Derynck, R. Nature (1995) [Pubmed]
  17. Antitumor activity of combined blockade of epidermal growth factor receptor and protein kinase A. Ciardiello, F., Damiano, V., Bianco, R., Bianco, C., Fontanini, G., De Laurentiis, M., De Placido, S., Mendelsohn, J., Bianco, A.R., Tortora, G. J. Natl. Cancer Inst. (1996) [Pubmed]
  18. Autocrine transforming growth factor alpha is dispensible for v-rasHa-induced epidermal neoplasia: potential involvement of alternate epidermal growth factor receptor ligands. Dlugosz, A.A., Cheng, C., Williams, E.K., Darwiche, N., Dempsey, P.J., Mann, B., Dunn, A.R., Coffey, R.J., Yuspa, S.H. Cancer Res. (1995) [Pubmed]
  19. Angiotensin II and EGF receptor cross-talk in chronic kidney diseases: a new therapeutic approach. Lautrette, A., Li, S., Alili, R., Sunnarborg, S.W., Burtin, M., Lee, D.C., Friedlander, G., Terzi, F. Nat. Med. (2005) [Pubmed]
  20. Growth retardation, duodenal lesions, and aberrant ileum architecture in triple null mice lacking EGF, amphiregulin, and TGF-alpha. Troyer, K.L., Luetteke, N.C., Saxon, M.L., Qiu, T.H., Xian, C.J., Lee, D.C. Gastroenterology (2001) [Pubmed]
  21. Blockade of epidermal growth factor receptor function by bivalent and monovalent fragments of 225 anti-epidermal growth factor receptor monoclonal antibodies. Fan, Z., Masui, H., Altas, I., Mendelsohn, J. Cancer Res. (1993) [Pubmed]
  22. Wa5 is a novel ENU-induced antimorphic allele of the epidermal growth factor receptor. Lee, D., Cross, S.H., Strunk, K.E., Morgan, J.E., Bailey, C.L., Jackson, I.J., Threadgill, D.W. Mamm. Genome (2004) [Pubmed]
  23. Effect of epidermal growth factor receptor internalization on regulation of the phospholipase C-gamma1 signaling pathway. Haugh, J.M., Schooler, K., Wells, A., Wiley, H.S., Lauffenburger, D.A. J. Biol. Chem. (1999) [Pubmed]
  24. Post-transcriptional control regulates transforming growth factor alpha in the human carcinoma KB cell line. Nicolini, G., Miloso, M., Moroni, M.C., Beguinot, L., Scotto, L. J. Biol. Chem. (1996) [Pubmed]
  25. Contribution of the transforming growth factor alpha B-loop beta-sheet to binding and activation of the epidermal growth factor receptor. Richter, A., Drummond, D.R., MacGarvie, J., Puddicombe, S.M., Chamberlin, S.G., Davies, D.E. J. Biol. Chem. (1995) [Pubmed]
  26. Synergistic interaction of transforming growth factor alpha and c-myc in mouse mammary and salivary gland tumorigenesis. Amundadottir, L.T., Johnson, M.D., Merlino, G., Smith, G.H., Dickson, R.B. Cell Growth Differ. (1995) [Pubmed]
  27. Intrapituitary regulatory system of mammotrophs in the mouse. Takahashi, S., Sharma, S., Oomizu, S., Honda, J., Takeuchi, S. Arch. Physiol. Biochem. (2002) [Pubmed]
  28. Excess biglycan causes eyelid malformation by perturbing muscle development and TGF-alpha signaling. Hayashi, Y., Liu, C.Y., Jester, J.J., Hayashi, M., Wang, I.J., Funderburgh, J.L., Saika, S., Roughley, P.J., Kao, C.W., Kao, W.W. Dev. Biol. (2005) [Pubmed]
  29. Profiles of novel diurnally regulated genes in mouse hypothalamus: Expression analysis of the cysteine and histidine-rich domain-containing, zinc-binding protein 1, the fatty acid-binding protein 7 and the GTPase, ras-like family member 11b. Gerstner, J.R., Vander Heyden, W.M., Lavaute, T.M., Landry, C.F. Neuroscience (2006) [Pubmed]
  30. Activation of the epidermal growth factor receptor signal transduction pathway stimulates tyrosine phosphorylation of protein kinase C delta. Denning, M.F., Dlugosz, A.A., Threadgill, D.W., Magnuson, T., Yuspa, S.H. J. Biol. Chem. (1996) [Pubmed]
  31. Multiple trophic actions of heparin-binding epidermal growth factor (HB-EGF) in the central nervous system. Kornblum, H.I., Zurcher, S.D., Werb, Z., Derynck, R., Seroogy, K.B. Eur. J. Neurosci. (1999) [Pubmed]
  32. Enhanced sensitivity to tumor growth and development in multistage skin carcinogenesis by transforming growth factor-alpha-induced epidermal growth factor receptor activation but not p53 inactivation. Shibata, M.A., Ward, J.M., Green, J.E., Merlino, G. Mol. Carcinog. (1997) [Pubmed]
  33. Transforming growth factor alpha up-regulates desmin expression during embryonic mouse tongue myogenesis. Yamane, A., Bringas, P., Mayo, M.L., Amano, O., Takahashi, K., Vo, H., Shum, L., Slavkin, H.C. Dev. Dyn. (1998) [Pubmed]
  34. Transforming growth factor-alpha regulates subpopulation of giant cells which secrete mouse placental lactogen-I (mPL-I) and/or mPL-II at midpregnancy. Yamaguchi, M., Ogura, K., Sakata, M., Miyake, A. J. Endocrinol. Invest. (1996) [Pubmed]
  35. Stimulation and inhibition of proliferation in the small intestinal crypts of the mouse after in vivo administration of growth factors. Potten, C.S., Owen, G., Hewitt, D., Chadwick, C.A., Hendry, H., Lord, B.I., Woolford, L.B. Gut (1995) [Pubmed]
  36. Simultaneous blockage of different EGF-like growth factors results in efficient growth inhibition of human colon carcinoma xenografts. De Luca, A., Arra, C., D'Antonio, A., Casamassimi, A., Losito, S., Ferraro, P., Ciardiello, F., Salomon, D.S., Normanno, N. Oncogene (2000) [Pubmed]
  37. Tumor necrosis factor regulation of apoptosis in mouse preimplantation embryos and its antagonism by transforming growth factor alpha/phosphatidylionsitol 3-kinase signaling system. Kawamura, K., Kawamura, N., Kumagai, J., Fukuda, J., Tanaka, T. Biol. Reprod. (2007) [Pubmed]
  38. Epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and basic fibroblast growth factor (bFGF) differentially influence neural precursor cells of mouse embryonic mesencephalon. Santa-Olalla, J., Covarrubias, L. J. Neurosci. Res. (1995) [Pubmed]
  39. A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. Reynolds, B.A., Tetzlaff, W., Weiss, S. J. Neurosci. (1992) [Pubmed]
  40. Transforming growth factor-alpha and epidermal growth factor receptor gene expression and action during pubertal development of the seminiferous tubule. Mullaney, B.P., Skinner, M.K. Mol. Endocrinol. (1992) [Pubmed]
  41. Establishment and characterization of a human gastric scirrhous carcinoma cell line in serum-free chemically defined medium. Yanagihara, K., Kamada, N., Tsumuraya, M., Amano, F. Int. J. Cancer (1993) [Pubmed]
  42. Lack of effects of transforming growth factor-alpha gene knockout on peripheral nerve regeneration may result from compensatory mechanisms. Xian, C.J., Li, L., Deng, Y.S., Zhao, S.P., Zhou, X.F. Exp. Neurol. (2001) [Pubmed]
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