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This study demonstrates that CCL22 and CCL17 stimulate pertussis toxin-sensitive elevation of intracellular calcium in the CEM leukemic T cell line and human peripheral blood-derived T helper type 2 (Th2) cells. Inhibition of phospholipase C (PLC) resulted in the abrogation of chemokine-mediated calcium mobilization. Chemokine-stimulated calcium responses were also abrogated completely by the inhibition of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptor-mediated calcium release. Chemotactic responses of CEM and human Th2 cells to CCL17 and CCL22 were similarly abrogated by inhibition of PLC and inhibition of novel, Ca2+-independent\/diacylglycerol-dependent protein kinase C (PKC) isoforms. Inhibition of Ins(1,4,5)P3 receptor-mediated calcium release from intracellular stores had no effect on chemotactic responses to CCR4 ligands. Taken together, this study provides compelling evidence of an important role for PLC and diacylglycerol-dependent effector mechanisms (most likely involving novel PKC isoforms) in CCL17- and CCL22-stimulated, directional cell migration. In this regard, CCL22 stimulates phosphatidylinositol-3 kinase-independent phosphorylation of the novel \u03b4 isoform of PKC at threonine 505, situated within its activation loop\u2014an event closely associated with increased catalytic activity.<\/jats:p>","DOI":"10.1189\/jlb.0106035","type":"journal-article","created":{"date-parts":[[2006,4,14]],"date-time":"2006-04-14T01:11:29Z","timestamp":1144977089000},"page":"1369-1380","source":"Crossref","is-referenced-by-count":48,"title":["Evidence that phospholipase C-dependent, calcium-independent mechanisms are required for directional migration of T lymphocytes in response to the CCR4 ligands CCL17 and CCL22"],"prefix":"10.1093","volume":"79","author":[{"given":"Darran G","family":"Cronshaw","sequence":"first","affiliation":[{"name":"Department of Pharmacy & Pharmacology, University of Bath , Claverton Down, Avon, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Kouroumalis","sequence":"additional","affiliation":[{"name":"Department of Pharmacy & Pharmacology, University of Bath , Claverton Down, Avon, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Parry","sequence":"additional","affiliation":[{"name":"Department of Pharmacy & Pharmacology, University of Bath , Claverton Down, Avon, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Pharmacy & Pharmacology, University of Bath , Claverton Down, Avon, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarin","family":"Brown","sequence":"additional","affiliation":[{"name":"Novartis Horsham Research Centre , West Sussex, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen G","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Pharmacy & Pharmacology, University of Bath , Claverton Down, Avon, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,4,13]]},"reference":[{"key":"2023033015240778900_cit-1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1124\/pr.54.2.227","article-title":"International Union of Pharmacology. 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