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Determination of the cell survival\u2010enhancing activity of growth factors by cell enumeration and neutral red uptake measurement gives equivalent results. PDGF displays a steep doseresponse relationship in the 1\u22125 ng\/ml range. The other factors display shallow log\u2010linear relationships in the following ranges: EGF: 0.2\u22125 ng\/ml; IGF\u20101: 2\u221280 ng\/ml; and insulin: 57\u22124,500 ng\/ml. Agonists that lead to the activation of protein kinase A, including forskolin, 8\u2010bromoadenosine 3\u2032:5\u2032\u2010cyclic monophosphate (Br\u2010cAMP) and N<jats:sup>6<\/jats:sup>,2\u2032\u2010O\u2010dibutyryladenosine 3\u2032:5\u2032\u2010cyclic monophosphate (db\u2010cAMP), markedly increase both short\u2010term (5\u2010h) and long\u2010term (20\u2010h) survival of cells. 2\u2010lsobutyl\u20101\u2010methylxanthine (IBMX) markedly enhances short\u2010term survival, but its effect decays with time. The protein kinase C agonist 12\u2010O\u2010tetradecanoyl phorbol\u201013\u2010acetate (TPA) has a moderate protective effect at concentrations of 16\u201032 nM, and 64 nM TPA is highly effective. The synthetic diacylglycerols 1,2\u2010dioctanoylglycerol (DiC<jats:sub>8<\/jats:sub>) and 1\u2010oleoyl\u20102\u2010acetylglycerol (OAG) and the calcium ionophore ionomycin show low activity. Supplemation of EGF with a protein kinase A or C agonist results in a varying additive increase in short\u2010term (5\u2010h) cell survival and supplementation of EGF+insulin or PDGF+EGF+insulin increases further the already high level of protection given by the growth factor combinations. Combining a protein kinase A and a protein kinase C agonist in the absence of growth factors gives an approximately additive increase in cell survival. Results obtained with kinase, RNA, and protein synthesis inhibitors suggest that: (1) activated protein kinase C catalyzes one or more phosphorylation events in quiescent Balb\/c\u20103T3 cells that lead to gene expression with the protein product(s) mediating protection of quiescent cells against death, and (2) phosphorylation events Catalyzed by protein kinase A largely serve to protect cells by a mechanism not requiring de novo RNA and protein biosynthesis.<\/jats:p>","DOI":"10.1002\/jcp.1041480111","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T08:07:46Z","timestamp":1109405266000},"page":"85-95","source":"Crossref","is-referenced-by-count":20,"title":["Activation of signal transduction pathways protects quiescent Balb\/c\u20103T3 fibroblasts against death due to serum deprivation"],"prefix":"10.1002","volume":"148","author":[{"given":"Igor","family":"Tamm","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toyoko","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0887-2333(87)90031-2"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2220195"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"13304","DOI":"10.1016\/S0021-9258(17)38870-1","article-title":"Growth factor\u2010stimulated protein phosphorylation in 3T3\u2010L1 cells","volume":"260","author":"Blackshear P. 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