{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:06:10Z","timestamp":1781103970890,"version":"3.54.1"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,10,29]]},"abstract":"<jats:p>\n                    The voltage-dependent and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated K\n                    <jats:sup>+<\/jats:sup>\n                    channel (MaxiK, BK) and the cellular proto-oncogene pp60\n                    <jats:sup>c-Src<\/jats:sup>\n                    (c-Src) are abundant proteins in vascular smooth muscle. The role of MaxiK channels as a vasorelaxing force is well established, but their role in vasoconstriction is unclear. Because Src participates in regulating vasoconstriction, we investigated whether c-Src inhibits MaxiK as a mechanism for agonist-induced vasoconstriction. Functional experiments in human and rat show that inhibitors of Src (Lavendustin A, PP2) but not inactive compounds (Lavendustin B, PP3) induce a pronounced relaxation of coronary or aortic smooth muscle precontracted with 5-hydroxytriptamine, phenylephrine, or Angiotensin II. Iberiotoxin, a MaxiK blocker, antagonizes the relaxation induced by Lavendustin A or PP2, indicating that c-Src inhibits the Iberiotoxin-sensitive component, likely MaxiK channels. In agreement, coronary muscle MaxiK currents were enhanced by Lavendustin A. To investigate the molecular mechanism of c-Src action on MaxiK channels, we transiently expressed its \u03b1 subunit, hSlo, with or without c-Src in HEK293T cells. The voltage sensitivity of hSlo was right-shifted by \u224816 mV. hSlo inhibition by c-Src is due to channel direct phosphorylation because: (\n                    <jats:italic>i<\/jats:italic>\n                    ) excised patches exposed to protein tyrosine phosphatase (CD45) resulted in a partial reversal of the inhibitory effect by \u224810 mV, and (\n                    <jats:italic>ii<\/jats:italic>\n                    ) immunoprecipitated hSlo channels were recognized by an anti-phosphotyrosine Ab. Furthermore, coexpression of hSlo and c-Src demonstrate a striking colocalization in HEK293T cells. We propose that MaxiK channels via direct c-Src-dependent phosphorylation play a significant role supporting vasoconstriction after activation of G protein-coupled receptors by vasoactive substances and neurotransmitters.\n                  <\/jats:p>","DOI":"10.1073\/pnas.222348099","type":"journal-article","created":{"date-parts":[[2002,10,29]],"date-time":"2002-10-29T12:24:11Z","timestamp":1035894251000},"page":"14560-14565","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":101,"title":["Coupling of c-Src to large conductance voltage- and Ca\n                    <sup>2+<\/sup>\n                    -activated K\n                    <sup>+<\/sup>\n                    channels as a new mechanism of agonist-induced vasoconstriction"],"prefix":"10.1073","volume":"99","author":[{"given":"Abderrahmane","family":"Alioua","sequence":"first","affiliation":[{"name":"Departments of Anesthesiology, Division of Molecular Medicine, and Molecular and Medical Pharmacology, and Physiology, and Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1778"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aman","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology, Division of Molecular Medicine, and Molecular and Medical Pharmacology, and Physiology, and Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1778"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhide","family":"Nishimaru","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology, Division of Molecular Medicine, and Molecular and Medical Pharmacology, and Physiology, and Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1778"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoud M.","family":"Zarei","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology, Division of Molecular Medicine, and Molecular and Medical Pharmacology, and Physiology, and Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1778"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Stefani","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology, Division of Molecular Medicine, and Molecular and Medical Pharmacology, and Physiology, and Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1778"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ligia","family":"Toro","sequence":"additional","affiliation":[{"name":"Departments of Anesthesiology, Division of Molecular Medicine, and Molecular and Medical Pharmacology, and Physiology, and Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1778"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,10,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1373909"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.211br.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5236.633"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.199br.x"},{"key":"e_1_3_3_5_2","first-page":"H1951","volume":"261","author":"Worley J. 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