{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:45:23Z","timestamp":1790048723524,"version":"4.0.1"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[1999,1]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014PYK2, a recently identified Ca\n            <jats:sup>2+<\/jats:sup>\n            -sensitive tyrosine kinase, has been implicated in extracellular signal-regulated kinase (ERK) activation via several G protein\u2013coupled receptors. We have reported that angiotensin II (Ang II) induces Ca\n            <jats:sup>2+<\/jats:sup>\n            -dependent transactivation of the epidermal growth factor receptor (EGFR) which serves as a scaffold for preactivated c-Src and downstream adaptors (Shc\/Grb2), leading to ERK activation in cultured rat vascular smooth muscle cells (VSMC). Herein we demonstrate the involvement of PYK2 in this cascade. Ang II rapidly induced tyrosine phosphorylation of PYK2, whose effect was completely inhibited by an AT\n            <jats:sub>1<\/jats:sub>\n            receptor antagonist and an intracellular Ca\n            <jats:sup>2+<\/jats:sup>\n            chelator. A Ca\n            <jats:sup>2+<\/jats:sup>\n            ionophore also induced PYK2 tyrosine phosphorylation to a level comparable with that by Ang II, whereas phorbol ester\u2013induced phosphorylation was less than that by Ang II. Moreover, PYK2 formed a complex coprecipitable with catalytically active c-Src after Ang II stimulation. Although a selective EGFR kinase inhibitor completely abolished Ang II\u2013induced recruitment of Grb2 to EGFR and markedly attenuated Ang II\u2013induced ERK activation, it had no effect on Ang II\u2013induced PYK2 tyrosine phosphorylation or its association with c-Src and Grb2. These data suggest that the AT\n            <jats:sub>1<\/jats:sub>\n            receptor uses Ca\n            <jats:sup>2+<\/jats:sup>\n            -dependent PYK2 to activate c-Src, thereby leading to EGFR transactivation, which preponderantly recruits Grb2 in rat VSMC.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.33.1.201","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"201-206","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":132,"title":["Involvement of PYK2 in Angiotensin II Signaling of Vascular Smooth Muscle Cells"],"prefix":"10.1161","volume":"33","author":[{"given":"Satoru","family":"Eguchi","sequence":"first","affiliation":[{"name":"From the 2nd Department of Internal Medicine, Tokyo Medical and Dental University (S.E., H.I., F.M., Y.H.), Tokyo 113, Japan; Department of Biochemistry, Vanderbilt University School of Medicine (SE, T.I., K.N., T.Y.), Nashville, Tenn; Department of Anatomy and Physiology, Meharry Medical College (E.D.M), Nashville, Tenn; and Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University (K.M.O.), Kyoto 607, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"From the 2nd Department of Internal Medicine, Tokyo Medical and Dental University (S.E., H.I., F.M., Y.H.), Tokyo 113, Japan; Department of Biochemistry, Vanderbilt University School of Medicine (SE, T.I., K.N., T.Y.), Nashville, Tenn; Department of Anatomy and Physiology, Meharry Medical College (E.D.M), Nashville, Tenn; and Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University (K.M.O.), Kyoto 607, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Inagami","sequence":"additional","affiliation":[{"name":"From the 2nd Department of Internal Medicine, Tokyo Medical and Dental University (S.E., H.I., F.M., Y.H.), Tokyo 113, Japan; Department of Biochemistry, Vanderbilt University School of Medicine (SE, T.I., K.N., T.Y.), Nashville, Tenn; Department of Anatomy and Physiology, Meharry Medical College (E.D.M), Nashville, Tenn; and Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University (K.M.O.), Kyoto 607, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Numaguchi","sequence":"additional","affiliation":[{"name":"From the 2nd Department of Internal Medicine, Tokyo Medical and Dental University (S.E., H.I., F.M., Y.H.), Tokyo 113, Japan; Department of Biochemistry, Vanderbilt University School of Medicine (SE, T.I., K.N., T.Y.), Nashville, Tenn; Department of Anatomy and Physiology, Meharry Medical College (E.D.M), Nashville, Tenn; and Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University (K.M.O.), Kyoto 607, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Yamakawa","sequence":"additional","affiliation":[{"name":"From the 2nd Department of Internal Medicine, Tokyo Medical and Dental University (S.E., H.I., F.M., Y.H.), Tokyo 113, Japan; Department of Biochemistry, Vanderbilt University School of Medicine (SE, T.I., K.N., T.Y.), Nashville, Tenn; Department of Anatomy and Physiology, Meharry Medical College (E.D.M), Nashville, Tenn; and Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University (K.M.O.), Kyoto 607, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangeline D.","family":"Motley","sequence":"additional","affiliation":[{"name":"From the 2nd Department of Internal Medicine, Tokyo Medical and Dental University (S.E., H.I., F.M., Y.H.), Tokyo 113, Japan; Department of Biochemistry, Vanderbilt University School of Medicine (SE, T.I., K.N., T.Y.), Nashville, Tenn; Department of Anatomy and Physiology, Meharry Medical College (E.D.M), Nashville, Tenn; and Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University (K.M.O.), Kyoto 607, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji M.","family":"Owada","sequence":"additional","affiliation":[{"name":"From the 2nd Department of Internal Medicine, Tokyo Medical and Dental University (S.E., H.I., F.M., Y.H.), Tokyo 113, Japan; Department of Biochemistry, Vanderbilt University School of Medicine (SE, T.I., K.N., T.Y.), Nashville, Tenn; Department of Anatomy and Physiology, Meharry Medical College (E.D.M), Nashville, Tenn; and Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University (K.M.O.), Kyoto 607, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiaki","family":"Marumo","sequence":"additional","affiliation":[{"name":"From the 2nd Department of Internal Medicine, Tokyo Medical and Dental University (S.E., H.I., F.M., Y.H.), Tokyo 113, Japan; Department of Biochemistry, Vanderbilt University School of Medicine (SE, T.I., K.N., T.Y.), Nashville, Tenn; Department of Anatomy and Physiology, Meharry Medical College (E.D.M), Nashville, Tenn; and Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University (K.M.O.), Kyoto 607, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Hirata","sequence":"additional","affiliation":[{"name":"From the 2nd Department of Internal Medicine, Tokyo Medical and Dental University (S.E., H.I., F.M., Y.H.), Tokyo 113, Japan; Department of Biochemistry, Vanderbilt University School of Medicine (SE, T.I., K.N., T.Y.), Nashville, Tenn; Department of Anatomy and Physiology, Meharry Medical College (E.D.M), Nashville, Tenn; and Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University (K.M.O.), Kyoto 607, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.62.4.3280155"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115881"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117033"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.73.3.8348686"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.72.6.8495553"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.29.1.366"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199606203342507"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.97.14.1411"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.80.5.607"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.15.8890"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/376737a0"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.36.21206"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.46.27742"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.47.29993"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/383547a0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.10.5680"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.134.1.8275937"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.24.14169"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.82.1.7"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.3.1711"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.32.19443"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/380541a0"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00413.x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.31.19125"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.27.17209"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.7.4637"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.40.24767"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.9.2574"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5276.792"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.3.1920"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.1.228"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3109\/10428199709059681"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.22.14341"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.33.1.201","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T17:36:56Z","timestamp":1715535416000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.33.1.201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,1]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1999,1]]}},"alternative-id":["10.1161\/01.HYP.33.1.201"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.33.1.201","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,1]]},"assertion":[{"value":"1998-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-10-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}