{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:10:23Z","timestamp":1791299423744,"version":"4.1.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,9,14]]},"abstract":"<jats:p>T-cell interactions with antigen-presenting cells are important for CD8 T-cell effector or memory fate determination. The integrin leukocyte function-associated antigen-1 (LFA-1) mediates T-cell adhesion but the contribution of LFA-1\u2013induced signaling pathways to T-cell responses is poorly understood. Here we demonstrate that proline-rich tyrosine kinase-2 (PYK2) deficiency impairs CD8 T-cell activation by synergistic LFA-1 and T-cell receptor stimulation. Furthermore, PYK2 is essential for LFA-1-mediated CD8 T-cell adhesion and LFA-1 costimulation of CD8 T-cell migration. During lymphocytic choriomeningitis virus infection in vivo, PYK2 deficiency results in a specific loss of short-lived effector CD8 T cells but does not affect memory-precursor CD8 T-cell development. Similarly, lack of LFA-1 primarily impairs the generation of short-lived effector cells. Thus, PYK2 facilitates LFA-1\u2013dependent CD8 T-cell responses and promotes CD8 T-cell short-lived effector fate, suggesting that PYK2 may be an interesting therapeutic target to suppress exacerbated CD8 T-cell responses.<\/jats:p>","DOI":"10.1073\/pnas.1011556107","type":"journal-article","created":{"date-parts":[[2010,8,30]],"date-time":"2010-08-30T22:49:18Z","timestamp":1283208558000},"page":"16234-16239","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":45,"title":["Proline-rich tyrosine kinase-2 is critical for CD8 T-cell short-lived effector fate"],"prefix":"10.1073","volume":"107","author":[{"given":"S\u00f6ren","family":"Beinke","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Rheumatology,"},{"name":"The Howard Hughes Medical Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyewon","family":"Phee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology,"},{"name":"The Howard Hughes Medical Institute,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Clingan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology,"},{"name":"Graduate Program in Biomedical Sciences, University of California, San Francisco, CA 94143-0795; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Schlessinger","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrdad","family":"Matloubian","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology,"},{"name":"Rosalind Russell Medical Research Center for Arthritis, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Rheumatology,"},{"name":"The Howard Hughes Medical Institute,"},{"name":"Rosalind Russell Medical Research Center for Arthritis, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,8,30]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141548"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2010.00899.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2010.00901.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/87720"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/87730"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.12.6833"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80461-6"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni908"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060928"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.7.4507"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07657"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5489.92"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139393"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.2.778"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04651"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1191"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.019117"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.133.4.895"},{"key":"e_1_3_3_19_2","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.4049\/jimmunol.162.2.1120","article-title":"Adhesion-dependent degranulation of neutrophils requires the Src family kinases Fgr and Hck","volume":"162","author":"M\u00f3csai A","year":"1999","unstructured":"A M\u00f3csai, E Ligeti, CA Lowell, G Berton, Adhesion-dependent degranulation of neutrophils requires the Src family kinases Fgr and Hck. J Immunol 162, 1120\u20131126 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200112113"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200404166"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00305-4"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00283-09"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900510106"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1549"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/383547a0"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.23.14301"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.7.1253"},{"key":"e_1_3_3_29_2","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.4049\/jimmunol.159.4.1753","article-title":"T cell receptor engagement induces tyrosine phosphorylation of FAK and Pyk2 and their association with Lck","volume":"159","author":"Berg NN","year":"1997","unstructured":"NN Berg, HL Ostergaard, T cell receptor engagement induces tyrosine phosphorylation of FAK and Pyk2 and their association with Lck. J Immunol 159, 1753\u20131757 (1997).","journal-title":"J Immunol"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.6.1055"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.1.228"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.3.791"},{"key":"e_1_3_3_33_2","doi-asserted-by":"crossref","first-page":"3652","DOI":"10.4049\/jimmunol.161.7.3652","article-title":"Stromal cell-derived factor-1 alpha and stem cell factor\/kit ligand share signaling pathways in hemopoietic progenitors: A potential mechanism for cooperative induction of chemotaxis","volume":"161","author":"Dutt P","year":"1998","unstructured":"P Dutt, JF Wang, JE Groopman, Stromal cell-derived factor-1 alpha and stem cell factor\/kit ligand share signaling pathways in hemopoietic progenitors: A potential mechanism for cooperative induction of chemotaxis. J Immunol 161, 3652\u20133658 (1998).","journal-title":"J Immunol"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1834348100"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/76882"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.6.1891"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.1.292"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199811)28:11<3867::AID-IMMU3867>3.0.CO;2-K"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199903)29:03<809::AID-IMMU809>3.0.CO;2-X"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80376-3"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.4.1415"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199901)29:01<45::AID-IMMU45>3.0.CO;2-I"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.04.019"},{"key":"e_1_3_3_44_2","doi-asserted-by":"crossref","first-page":"5375","DOI":"10.4049\/jimmunol.157.12.5375","article-title":"Impaired immune responses toward alloantigens and tumor cells but normal thymic selection in mice deficient in the beta2 integrin leukocyte function-associated antigen-1","volume":"157","author":"Shier P","year":"1996","unstructured":"P Shier, et al., Impaired immune responses toward alloantigens and tumor cells but normal thymic selection in mice deficient in the beta2 integrin leukocyte function-associated antigen-1. J Immunol 157, 5375\u20135386 (1996).","journal-title":"J Immunol"},{"key":"e_1_3_3_45_2","doi-asserted-by":"crossref","first-page":"4826","DOI":"10.4049\/jimmunol.163.9.4826","article-title":"Defective CD8+ T cell activation and cytolytic function in the absence of LFA-1 cannot be restored by increased TCR signaling","volume":"163","author":"Shier P","year":"1999","unstructured":"P Shier, K Ngo, WP Fung-Leung, Defective CD8+ T cell activation and cytolytic function in the absence of LFA-1 cannot be restored by increased TCR signaling. J Immunol 163, 4826\u20134832 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071641"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.12.016"},{"key":"e_1_3_3_48_2","doi-asserted-by":"crossref","first-page":"5029","DOI":"10.4049\/jimmunol.163.9.5029","article-title":"Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration","volume":"163","author":"Ding ZM","year":"1999","unstructured":"ZM Ding, et al., Relative contribution of LFA-1 and Mac-1 to neutrophil adhesion and migration. J Immunol 163, 5029\u20135038 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1868"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1011556107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T19:41:51Z","timestamp":1711741311000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1011556107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8,30]]},"references-count":49,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2010,9,14]]}},"alternative-id":["10.1073\/pnas.1011556107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1011556107","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,8,30]]},"assertion":[{"value":"2010-08-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}