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Here we show that TGF\u03b21 evokes robust phosphorylation of Akt\/PKB, a protein kinase dependent on the products of phosphatidylinositol 3-OH kinase (PI3K). TGF\u03b21-evoked stimulation of K<jats:sub>Ca<\/jats:sub>channels is blocked by the PI3K inhibitors wortmannin and LY294002. These drugs also inhibit TGF\u03b21 effects on Akt\/PKB phosphorylation but have no effect on TGF\u03b21-evoked Erk activation. Application of the MEK1 inhibitor PD98059 blocked TGF\u03b21 effects on Erk but had no effect on Akt\/PKB phosphorylation. These results indicate that PI3K and Erk represent parallel signaling cascades activated by TGF\u03b21 in ciliary neurons. The effects of TGF\u03b21 on functional expression of K<jats:sub>Ca<\/jats:sub>are blocked by the microtubule inhibitors colchicine and nocodazole, by botulinum toxins A and E, and by brefeldin-A, an agent that disrupts the Golgi apparatus. These data indicate that translocation of a membrane protein, possibly Slowpoke (SLO), is required for the acute posttranslational effects of TGF\u03b21 on K<jats:sub>Ca<\/jats:sub>channels. Confocal immunofluorescence studies with three different SLO antisera showed robust expression of SLO in multiple intracellular compartments of embryonic day 9\u201313 ciliary neurons, including the cell nucleus. These data suggest that TGF\u03b21 evokes insertion of SLO channels into the plasma membrane as a result of signaling cascades that entail activation of Erk and PI3K.<\/jats:p>","DOI":"10.1152\/jn.2002.88.2.954","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T19:55:37Z","timestamp":1513886137000},"page":"954-964","source":"Crossref","is-referenced-by-count":45,"title":["Developmental Regulation of Neuronal K<sub>Ca<\/sub>Channels by TGF\u03b21: An Essential Role for PI3 Kinase Signaling and Membrane Insertion"],"prefix":"10.1152","volume":"88","author":[{"given":"Loic","family":"Lhuillier","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204-5513"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart E.","family":"Dryer","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry, University of Houston, Houston, Texas 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