Phosphatidylinositol transfer proteins and protein kinase C make separate but non-interacting contributions to the phosphorylation state necessary for secretory competence in rat mast cells

The Biochemical Journal
J A PinxterenG M Thomas

Abstract

Mast cells permeabilized by streptolysin O undergo exocytosis when stimulated with Ca(2+) and guanosine 5'-[gamma-thio]triphosphate but become progressively refractory to this stimulus if it is delayed. This run-down of responsiveness occurs over a period of 20-30 min, during which the cells leak soluble and tethered proteins. We show here that withdrawal of ATP during the process of run-down is strongly inhibitory but that as little as 25 microM ATP can extend responsiveness significantly; this effect is maximal at 50 microM. When phosphatidylinositol transfer proteins (PITPs) are provided to cells at the time of permeabilization, run-down is retarded. We conclude that in the presence of ATP they convey substrates for phosphorylation that are essential for exocytosis and thus interact with the regulatory machinery. Furthermore, we show that PITPalpha and PITPbeta have additive effects in this mechanism, suggesting that they are not functionally redundant. Alternatively, secretion from run-down cells can be inhibited by the aminoglycoside antibiotic neomycin, which is understood to bind to phosphoinositide headgroups, and by a PH (pleckstrin homology) domain polypeptide that binds phosphoinositides. The apparent displacement of...Continue Reading

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Citations

Jun 14, 2005·Pharmacology & Therapeutics·Paige Lacy
Mar 22, 2002·Molecular Biology of the Cell·James G AlbVytas A Bankaitis
Jan 17, 2015·Biochimica Et Biophysica Acta·Aby GrabonVytas A Bankaitis
Jul 13, 2021·Frontiers in Immunology·Lubica DraberovaPetr Draber

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