{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T14:51:51Z","timestamp":1770475911738,"version":"3.49.0"},"reference-count":89,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,3,5]],"date-time":"2003-03-05T00:00:00Z","timestamp":1046822400000},"content-version":"vor","delay-in-days":32,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunological Reviews"],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:title>Summary:<\/jats:title><jats:p>Shc is a prototype adapter protein that is expressed from the earliest stages of T\u2010cell development. Shc becomes rapidly tyrosine phosphorylated after T\u2010cell receptor (TCR) engagement. Expression of dominant negative forms of Shc in T\u2010cell lines had also suggested a role for this adapter downstream of the TCR. However, until recently, the relative significance of Shc compared to several other adapters in T cells was unclear. Mice lacking Shc expression specifically in the T\u2010cell lineage together with inducible expression of dominant negative Shc in transgenic mice have revealed an essential and nonredundant role for Shc in thymic T\u2010cell development. Functional defects in a Jurkat T\u2010cell line lacking Shc expression also suggest a role for Shc in mature T\u2010cell functions. While the requirement of Shc in T\u2010cell signaling is now established, precisely what signaling pathways downstream of Shc make this adapter unique are less clear. Although the Shc\u2010mediated activation of the extracellular signal regulated kinase (Erk)\/mitogen\u2010activated protein kinase (MAPK) pathway could be one component, Shc likely signals to other pathways in T cells that are not yet discovered. A better molecular understanding of Shc function in the future could provide insights into how multiple adapters coordinate the various outcomes downstream of the TCR.<\/jats:p>","DOI":"10.1034\/j.1600-065x.2003.00025.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T02:35:43Z","timestamp":1047436543000},"page":"183-195","source":"Crossref","is-referenced-by-count":15,"title":["Role of Shc in T\u2010cell development and function"],"prefix":"10.1111","volume":"191","author":[{"given":"Li","family":"Zhang","sequence":"first","affiliation":[]},{"given":"Ulrike","family":"Lorenz","sequence":"additional","affiliation":[]},{"given":"Kodi S.","family":"Ravichandran","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2003,3,5]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1999.0179"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)80040-5"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80315-5"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214842"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010927208180"},{"key":"e_1_2_6_7_2","doi-asserted-by":"crossref","unstructured":"SedwickCE AltmanA.Ordered just so: lipid rafts and lymphocyte function. Sci STKE 2002; RE22002.","DOI":"10.1126\/stke.2002.122.re2"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90334-4"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(02)00345-X"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(00)00221-1"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90598-7"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1995.0027"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.092601.111357"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(01)79003-7"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01716-3"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.17.1.89"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202337"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)80017-7"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90536-L"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204776"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(00)00146-5"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1515\/BC.1999.020"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/378584a0"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.17.7784"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00700.x"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(01)02154-7"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.9.4810"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.9.1132"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8235613"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.11.5275"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.7.4435"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082647499"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199808)28:08<2265::AID-IMMU2265>3.0.CO;2-P"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.7.4087"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(96)00748-8"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01008.x"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.4.1824"},{"key":"e_1_2_6_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.5.2586"},{"key":"e_1_2_6_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.32.20487"},{"key":"e_1_2_6_40_2","first-page":"767","article-title":"The aminoterminal phosphotyrosine binding domain of Shc associates with ZAP\u201070 and mediates TCR dependent gene activation","volume":"13","author":"Milia E","year":"1996","journal-title":"Oncogene"},{"key":"e_1_2_6_41_2","doi-asserted-by":"crossref","first-page":"17659","DOI":"10.1016\/S0021-9258(17)46751-2","article-title":"Interleukin\u20102\u2010induced tyrosine phos\u2010phorylation of p52shc in T lymphocytes","volume":"268","author":"Burns LA","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_2_6_42_2","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.4049\/jimmunol.159.8.3767","article-title":"Selective binding of shc\u2010SH2 domain to tyrosine\u2010phosphorylated \u03b6\u2010 but not \u03b3\u2010chain upon CD16 ligation on human NK cells","volume":"159","author":"Galandrini R","year":"1997","journal-title":"J Immunol"},{"key":"e_1_2_6_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.23.13981"},{"key":"e_1_2_6_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5265.1170"},{"key":"e_1_2_6_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203451"},{"key":"e_1_2_6_46_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST0290377"},{"key":"e_1_2_6_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.9.5540"},{"key":"e_1_2_6_48_2","first-page":"615","article-title":"The role of p21ras in receptor tyrosine kinase signaling","volume":"4","author":"Medema RH","year":"1993","journal-title":"Crit Rev Oncog"},{"key":"e_1_2_6_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00428-7"},{"key":"e_1_2_6_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb26663.x"},{"key":"e_1_2_6_51_2","doi-asserted-by":"publisher","DOI":"10.1385\/IR:21:2-3:71"},{"key":"e_1_2_6_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90401-8"},{"key":"e_1_2_6_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/79713"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)80024-7"},{"key":"e_1_2_6_55_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1998.tb01234.x"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(00)01744-8"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00316-3"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(00)00209-0"},{"key":"e_1_2_6_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni820"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.14.6232"},{"key":"e_1_2_6_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200001)30:1<8::AID-IMMU8>3.0.CO;2-8"},{"key":"e_1_2_6_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00227-8"},{"key":"e_1_2_6_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/13.1.105"},{"key":"e_1_2_6_64_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7660125"},{"key":"e_1_2_6_65_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.8.1093"},{"key":"e_1_2_6_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80032-1"},{"key":"e_1_2_6_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/6.7.995"},{"key":"e_1_2_6_68_2","doi-asserted-by":"publisher","DOI":"10.1159\/000060549"},{"key":"e_1_2_6_69_2","doi-asserted-by":"publisher","DOI":"10.1385\/IR:23:2-3:157"},{"key":"e_1_2_6_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(95)80023-9"},{"key":"e_1_2_6_71_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb26671.x"},{"key":"e_1_2_6_72_2","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1016\/S0021-9258(17)42066-7","article-title":"The adapter protein Shc interacts with the interleukin\u20102 (IL\u20102) receptor upon IL\u20102 stimulation","volume":"269","author":"Ravichandran KS","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_6_73_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.5.2077"},{"key":"e_1_2_6_74_2","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.4049\/jimmunol.161.9.4627","article-title":"The IL\u20102 receptor promotes proliferation, bcl\u20102 and bcl\u2010x induction, but not cell viability through the adapter molecule Shc","volume":"161","author":"Lord JD","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_6_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80103-X"},{"key":"e_1_2_6_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.19.7109-7120.2000"},{"key":"e_1_2_6_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0802-710"},{"key":"e_1_2_6_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/46311"},{"key":"e_1_2_6_79_2","first-page":"728","article-title":"Selective expression and constitutive phosphorylation of SHC proteins in the CD34+ fraction of chronic myelogenous leukemias","volume":"60","author":"Bonati A","year":"2000","journal-title":"Cancer Res"},{"key":"e_1_2_6_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80054-0"},{"key":"e_1_2_6_81_2","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1182\/blood.V82.8.2296.2296","article-title":"Erythropoietin stimulates the tyrosine phosphorylation of Shc and its association with Grb2 and a 145\u2010Kd tyrosine phosphorylated protein","volume":"82","author":"Damen JE","year":"1993","journal-title":"Blood"},{"key":"e_1_2_6_82_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.16.10396"},{"key":"e_1_2_6_83_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.7.1333"},{"key":"e_1_2_6_84_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.11.1610"},{"key":"e_1_2_6_85_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202507"},{"key":"e_1_2_6_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80577-4"},{"key":"e_1_2_6_87_2","volume-title":"Sci STKE","author":"Sedwick CE","year":"2002"},{"key":"e_1_2_6_88_2","doi-asserted-by":"publisher","DOI":"10.1078\/1438-4221-00150"},{"key":"e_1_2_6_89_2","doi-asserted-by":"publisher","DOI":"10.1038\/35020093"},{"key":"e_1_2_6_90_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5375.416"}],"container-title":["Immunological Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1034%2Fj.1600-065X.2003.00025.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1034\/j.1600-065X.2003.00025.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T18:14:15Z","timestamp":1697220855000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1034\/j.1600-065X.2003.00025.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,2]]},"references-count":89,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,2]]}},"alternative-id":["10.1034\/j.1600-065X.2003.00025.x"],"URL":"https:\/\/doi.org\/10.1034\/j.1600-065x.2003.00025.x","archive":["Portico"],"relation":{},"ISSN":["0105-2896","1600-065X"],"issn-type":[{"value":"0105-2896","type":"print"},{"value":"1600-065X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,2]]}}}