Calcium regulates inositol 1,3,4,5‐tetrakisphosphate production in lysed thymocytes and in intact cells stimulated with concanavalin A

• Published in: The EMBO journal Vol. 6; no. 4; pp. 957 - 962
• Main Authors: Zilberman, Y., Howe, L.R., Moore, J.P., Hesketh, T.R., Metcalfe, J.C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.04.1987
• Subjects: Animals; Biological and medical sciences; calcium; Calcium - pharmacology; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cytosol - metabolism; Fundamental and applied biological sciences. Psychology; Guanosine 5'-O-(3-Thiotriphosphate); Guanosine Triphosphate - analogs & derivatives; Guanosine Triphosphate - pharmacology; inositol 1,3,4,5-tetrakisphosphate; Inositol Phosphates - biosynthesis; Kinetics; Lymphocyte Activation; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes - metabolism; Mice; Mice, Inbred BALB C; Molecular and cellular biology; Sugar Phosphates - biosynthesis; Thionucleotides - pharmacology; thymus; Calcium; Thymocyte; Rodentia; Activation; Concanavalin A; Vertebrata; Regulation(control); Mammalia; Mouse; Animal; Inositophospholipide; Mitogen; Mechanism of action
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1987.tb04845.x

Lysed mouse thymocytes release [3H]inositol 1,4,5 trisphosphate from [3H]inositol‐labelled phosphatidyl inositol 4,5‐bisphosphate in response to GTP gamma S, and rapidly phosphorylate [3H]inositol 1,4,5‐trisphosphate to [3H]inositol 1,3,4,5‐tetrakisphosphate. The rate of phosphorylation is increased approximately 7‐fold when the free [Ca2+] in the lysate is increased from 0.1 to 1 microM, the range in which the cytosolic free [Ca2+] increases in intact thymocytes in response to the mitogen concanavalin A. Stimulation of the intact cells with concanavalin A also results in a rapid and sustained increase in the amount of inositol 1,3,4,5‐tetrakisphosphate, and a much smaller transient increase in 1,4,5‐trisphosphate. Lowering [Ca2+] in the medium from 0.4 mM to 0.1 microM before addition of concanavalin A reduces accumulation of inositol 1,3,4,5‐tetrakisphosphate by at least 3‐fold whereas the increase in inositol 1,4,5‐trisphosphate is sustained rather than transient. The data imply that in normal medium the activity of the inositol 1,4,5‐trisphosphate kinase increases substantially in response to the rise in cytosolic free [Ca2+] generated by concanavalin A, accounting for both the transient accumulation of inositol 1,4,5‐trisphosphate and the sustained high levels of inositol 1,3,4,5‐tetrakisphosphate. Inositol 1,3,4,5‐tetrakisphosphate is a strong candidate for the second messenger for Ca2+ entry across the plasma membrane. This would imply that the inositol polyphosphates regulate both Ca2+ entry and intracellular Ca2+ release, with feedback control of the inositol polyphosphate levels by Ca2+.