{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T05:02:35Z","timestamp":1770440555822,"version":"3.49.0"},"reference-count":32,"publisher":"The Company of Biologists","issue":"Supplement_13","license":[{"start":{"date-parts":[[1990,1,1]],"date-time":"1990-01-01T00:00:00Z","timestamp":631152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1990,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>int-2 was discovered as a proto-oncogene transcriptionally activated by MMTV proviral insertion during mammary tumorigenesis in the mouse. Sequence analysis showed int-2 to be a member of the fibroblast growth factor family of genes. In normal breast and most other adult mouse tissues, int-2 expression was not detected except for low levels in brain and testis. However, using in situ hybridization, expression was found at a number of sites during embryonic development, from day 7 until birth. An analysis of the int-2 transcripts found in embryonal carcinoma cells revealed six major classes of RNA initiating at three promoters and terminating at either of two polyadenylation sites. Despite the transcriptional complexities, all size classes of RNA encompass the same open reading frame. Using an SV40 early promoter to drive transcription of an int-2 cDNA in COS-1 cells, several proteins were observed. These were shown to be generated by initiation from either of two codons: One, a CUG, leads to a product which localizes extensively to the cell nucleus and partially to the secretory pathway. In contrast, initiation at a downstream AUG codon results in quantitative translocation across the endoplasmic reticulum and the accumulation of products ranging in size from 27.5\u00d7103Mr to 31.5\u00d7103Mr in organelles of the secretory pathway. These proteins represented glycosylated and non-glycosylated forms of the same primary product with or without the signal peptide removed. These findings suggest the potential for a dual role of int-2-, an autocrine function acting at the cell nucleus, and a possible paracrine action through a secreted product.<\/jats:p>","DOI":"10.1242\/jcs.1990.supplement_13.9","type":"journal-article","created":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T12:23:44Z","timestamp":1369311824000},"page":"87-96","source":"Crossref","is-referenced-by-count":22,"title":["Characterization of INT-2: A member of the fibroblast growth factor family"],"prefix":"10.1242","volume":"1990","author":[{"given":"Clive","family":"Dickson","sequence":"first","affiliation":[{"name":"1 Laboratories of Viral Carcinogenesis and Molecular Oncology, Lincoln\u2019s Inn Fields, London WC2A 3PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piers","family":"Acland","sequence":"additional","affiliation":[{"name":"1 Laboratories of Viral Carcinogenesis and Molecular Oncology, Lincoln\u2019s Inn Fields, London WC2A 3PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalind","family":"Smith","sequence":"additional","affiliation":[{"name":"1 Laboratories of Viral Carcinogenesis and Molecular Oncology, Lincoln\u2019s Inn Fields, London WC2A 3PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Dixon","sequence":"additional","affiliation":[{"name":"1 Laboratories of Viral Carcinogenesis and Molecular Oncology, Lincoln\u2019s Inn Fields, London WC2A 3PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Deed","sequence":"additional","affiliation":[{"name":"2 Laboratories of Viral Carcinogenesis, Imperial Cancer Research Fund, Lincoln\u2019s Inn Fields, London WC2A 3PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Macallan","sequence":"additional","affiliation":[{"name":"2 Laboratories of Viral Carcinogenesis, Imperial Cancer Research Fund, Lincoln\u2019s Inn Fields, London WC2A 3PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Walther","sequence":"additional","affiliation":[{"name":"2 Laboratories of Viral Carcinogenesis, Imperial Cancer Research Fund, Lincoln\u2019s Inn Fields, London WC2A 3PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances","family":"Fuller-Pace","sequence":"additional","affiliation":[{"name":"1 Laboratories of Viral Carcinogenesis and Molecular Oncology, Lincoln\u2019s Inn Fields, London WC2A 3PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Kiefer","sequence":"additional","affiliation":[{"name":"1 Laboratories of Viral Carcinogenesis and Molecular Oncology, Lincoln\u2019s Inn Fields, London WC2A 3PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon","family":"Peters","sequence":"additional","affiliation":[{"name":"2 Laboratories of Viral Carcinogenesis, Imperial Cancer Research Fund, Lincoln\u2019s Inn Fields, London WC2A 3PX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1990,1,1]]},"reference":[{"key":"2024071019513764100_JOCES_1990_S13_87C1","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1002\/j.1460-2075.1986.tb04530.x","article-title":"Human basic fibroblast growth factor: nucleotide sequence and genomic organization","volume":"5","author":"Abraham","year":"1986","journal-title":"EMBO J."},{"key":"2024071019513764100_JOCES_1990_S13_87C2","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/343662a0","article-title":"Subcellular fate of the int-2 oncoprotein is determined by choice of initiation codon","volume":"343","author":"Acland","year":"1990","journal-title":"Nature"},{"key":"2024071019513764100_JOCES_1990_S13_87C3","first-page":"129","article-title":"Addition of growth hormone secretion signal to basic fibroblast growth factor results in cell transformation and secretion of aberrant forms of the protein","volume":"3","author":"Blam","year":"1988","journal-title":"Oncogene"},{"key":"2024071019513764100_JOCES_1990_S13_87C4","first-page":"429","article-title":"Sequence organization of the human int-2 gene and its expression in teratocarcinoma cells","volume":"4","author":"Brookes","year":"1989","journal-title":"Oncogene"},{"key":"2024071019513764100_JOCES_1990_S13_87C5","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev.bi.58.070189.003043","article-title":"The heparin binding (fibroblast) growth factor family proteins. A","volume":"58","author":"Burgess","year":"1989","journal-title":"Rev. Biochem."},{"key":"2024071019513764100_JOCES_1990_S13_87C6","doi-asserted-by":"crossref","first-page":"5660","DOI":"10.1073\/pnas.84.16.5660","article-title":"Isolation of a rearranged human transforming gene following transfection of Kaposi sarcoma DNA","volume":"84","author":"Delli-Bovi","year":"1987","journal-title":"Proc. natn. Acad. Sci. 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