Receptor specificity of growth factor-stimulated synthesis of 3-phosphorylated inositol lipids in Swiss 3T3 cells

  • Jackson T
  • Stephens L
  • Hawkins P
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We have investigated synthesis of 3-phosphorylated inositol lipids in growth factor-stimulated Swiss 3T3 cells. Those growth factors tested which act via tyrosine kinase-containing receptors (platelet-derived growth factor (PDGF), insulin growth factor I (IGF-I), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF)) caused the rapid synthesis of [32P]PtdIns(3,4)P2 and [32P]PtdIns(3,4,5)P3 (PtdIns is phosphatidylinositol) in [32P]P(i)-prelabeled cells and the appearance of an inositol lipid 3-OH kinase in antiphosphotyrosine immunoprecipates. In contrast, those growth factors tested which act via G-protein-coupled receptors (bombesin, vasopressin, prostaglandin E1) were unable to stimulate either of the above responses. Furthermore, while PDGF was able to increase the formation of PtdIns(3,4)P2 and PtdIns(3,4,5)P3 in streptolysin-permeabilized cells, guanosine 5'-3-(thio)triphosphate and guanyl-5'-yl imidodiphosphate were not. These results suggest that Swiss 3T3 cells possess the machinery for tyrosine kinase but not G-protein-mediated activation of PtdIns(4,5)P2 3-OH kinase; a situation which is the inverse to that recently described for human neutrophils. The tyrosine kinase-containing receptors differed markedly in their relative abilities to elevate the levels of [32P] PtdIns(3,4,5)P3 (ranked in the order PDGF greater than or equal to IGF-I greater than EGF greater than bFGF), [32P]Ptd-OH (PDGF greater than EGF greater than bFGF; undetectable for IGF-I), and [32P]PtdIns4P (EGF greater than bFGF greater than PDGF; undetectable for IGF-I) in [32P]P(i)-prelabeled cells. These differences are epitomized by IGF-I, which was the joint most powerful stimulus for [32P] PtdIns(3,4,5)P3 formation, but was unable to stimulate a measurable accumulation of [32P]Ptd-OH (and hence, by deduction, was unable to stimulate phospholipase C). These results indicate that there is a differential ability among the tyrosine kinase-containing receptors present in a single cell to recruit phospholipase C and PtdIns(4,5)P2 3-OH kinase into their signalling complexes and further emphasizes the notion that the rapid synthesis of PtdIns(3,4,5)P3 may be a signalling event.

Author-supplied keywords

  • 1-Phosphatidylinositol 3-Kinase
  • 1-Phosphatidylinositol 4-Kinase
  • 3T3 Cells
  • Alprostadil/pharmacology
  • Animal
  • Bombesin/pharmacology
  • Cell Surface/drug effects/*physiology
  • Epidermal Growth Factor/pharmacology
  • Fibroblast Growth Factor 2/pharmacology
  • Growth Substances/*pharmacology
  • Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology
  • Guanylyl Imidodiphosphate/pharmacology
  • Hormones/*pharmacology
  • Inositol Phosphates/isolation & purification/*meta
  • Insulin-Like Growth Factor I/pharmacology
  • Insulin/pharmacology
  • Kinetics
  • Mice
  • Non-U.S. Gov't
  • Phosphates/metabolism
  • Phosphorus Radioisotopes
  • Phosphotransferases/*metabolism
  • Platelet-Derived Growth Factor/pharmacology
  • Receptors
  • Support
  • Tetradecanoylphorbol Acetate/pharmacology
  • Vasopressins/pharmacology

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  • Trevor R Jackson

  • Leonard R Stephens

  • P T Hawkins

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