{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:26:54Z","timestamp":1789882014590,"version":"4.0.1"},"reference-count":59,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T00:00:00Z","timestamp":1392595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:p>Activated forms of the platelet derived growth factor receptor alpha (PDGFR\u03b1) have been described in various tumors, including FIP1L1\u2010PDGFR\u03b1 in patients with myeloproliferative diseases associated with hypereosinophilia and the PDGFR\u03b1<jats:sup>D842V<\/jats:sup> mutant in gastrointestinal stromal tumors and inflammatory fibroid polyps.<\/jats:p><jats:p>To gain a better insight into the signal transduction mechanisms of PDGFR\u03b1 oncogenes, we mutated twelve potentially phosphorylated tyrosine residues of FIP1L1\u2010PDGFR\u03b1 and identified three mutations that affected cell proliferation. In particular, mutation of tyrosine 720 in FIP1L1\u2010PDGFR\u03b1 or PDGFR\u03b1<jats:sup>D842V<\/jats:sup> inhibited cell growth and blocked ERK signaling in Ba\/F3 cells. This mutation also decreased myeloproliferation in transplanted mice and the proliferation of human CD34<jats:sup>+<\/jats:sup> hematopoietic progenitors transduced with FIP1L1\u2010PDGFR\u03b1. We showed that the non\u2010receptor protein tyrosine phosphatase SHP2 bound directly to tyrosine 720 of FIP1L1\u2010PDGFR\u03b1. SHP2 knock\u2010down decreased proliferation of Ba\/F3 cells transformed with FIP1L1\u2010PDGFR\u03b1 and PDGFR\u03b1<jats:sup>D842V<\/jats:sup> and affected ERK signaling, but not STAT5 phosphorylation. Remarkably, SHP2 was not essential for cell proliferation and ERK phosphorylation induced by the wild\u2010type PDGF receptor in response to ligand stimulation, suggesting a shift in the function of SHP2 downstream of oncogenic receptors.<\/jats:p><jats:p>In conclusion, our results indicate that SHP2 is required for cell transformation and ERK activation by mutant PDGF receptors.<\/jats:p>","DOI":"10.1016\/j.molonc.2014.02.003","type":"journal-article","created":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T17:48:48Z","timestamp":1392659328000},"page":"728-740","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The tyrosine phosphatase SHP2 is required for cell transformation by the receptor tyrosine kinase mutants FIP1L1\u2010PDGFR\u03b1 and PDGFR\u03b1 D842V"],"prefix":"10.1002","volume":"8","author":[{"given":"Laura A.","family":"No\u00ebl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence A.","family":"Arts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen P.","family":"Montano-Almendras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luk","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Gielen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Toffalini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Y.","family":"Marbehant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Cools","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Baptiste","family":"Demoulin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306758200"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1653708"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306461200"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.16.12.6926"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.15.7335"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4183"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-008-9126-y"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207471"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210572200"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa025217"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00108-9"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.14.068"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2007.10.002"},{"key":"e_1_2_8_15_1","first-page":"3971","article-title":"STAT5 activation is required for interleukin-9-dependent growth and transformation of lymphoid cells","volume":"60","author":"Demoulin J.B.","year":"2000","journal-title":"Cancer Res."},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0533"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-286757"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","unstructured":"Ezeokonkwo C. Zhelkovsky A. Lee R. Bohm A. Moore C.L. A flexible linker region in Fip1 is needed for efficient mRNA polyadenylation. Rna 17 652\u2013664.","DOI":"10.1261\/rna.2273111"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80785-0"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08505-7"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3399"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079666"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-419X(98)00015-8"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2012.04203.x"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312996200"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05088.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-365726"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.2"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/195239"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.5.1701"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00369-0"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-375873"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn099"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.13"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.040147"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07294.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.23.16619"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.047530"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-504340"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.308"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(03)00091-4"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.7.2897"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701797200"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202705"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1994.00029.x"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.18.5321"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601192103"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808058200"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi051408h"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0000052"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-279752"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.076638"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2008.001149"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8902"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201555"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-209262"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.218"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202513"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.2741\/3051"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(04)00050-4"}],"container-title":["Molecular Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.molonc.2014.02.003","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.molonc.2014.02.003","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S1574789114000398?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S1574789114000398?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.molonc.2014.02.003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T13:36:22Z","timestamp":1695476182000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1016\/j.molonc.2014.02.003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2,17]]},"references-count":59,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.1016\/j.molonc.2014.02.003"],"URL":"https:\/\/doi.org\/10.1016\/j.molonc.2014.02.003","archive":["Portico"],"relation":{},"ISSN":["1574-7891","1878-0261"],"issn-type":[{"value":"1574-7891","type":"print"},{"value":"1878-0261","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2,17]]},"assertion":[{"value":"2013-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-02-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}