Inhibition by staurosporine of mitogen-induced calcium mobilisation in human T lymphoblasts

Stephen G. Ward; Doreen Cantrell; John Westwick

doi:10.1016/0014-5793(88)80952-9

Inhibition by staurosporine of mitogen-induced calcium mobilisation in human T lymphoblasts

Stephen G. Ward
, Doreen Cantrell
, John Westwick

Cell Signalling and Immunology

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Addition of monoclonal antibodies (UCHT1) directed against the antigen receptor/CD3 complex or the addition of the mitogens concanavalin A or phytohemagglutinin to human T lymphoblasts induced an elevation of the cytosolic free calcium concentration ([Ca²⁺]_i) as monitored by the fluorescence of the intracellular fura-2. The rise in [Ca²⁺]_i induced by these agents was effectively inhibited by staurosporine, an agent which inhibits protein kinase (PK)C and PKA. Conversely the PKC activator 12-O-tetradecanoyl phorbol-13-acetate decreased the delay and accelerated the rate of elevation of [Ca²⁺]_i induced by the mitogens and UCHT1. Increasing the concentration of cAMP or cGMP in the T lymphoblasts had no effect on agonist-induced elevation of [Ca²⁺]_i. Our data indicate that PKC can exert a positive feedback on the level of cytosolic Ca²⁺ in T lymphocytes, in contrast to what has been observed with other cells.

Original language	English
Pages (from-to)	363-366
Number of pages	4
Journal	FEBS Letters
Volume	239
Issue number	2
DOIs	https://doi.org/10.1016/0014-5793(88)80952-9
Publication status	Published - 7 Nov 1988

Keywords

Ca
Fura-2
Staurosporine
T lymphocyte

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/0014-5793(88)80952-9

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title = "Inhibition by staurosporine of mitogen-induced calcium mobilisation in human T lymphoblasts",

abstract = "Addition of monoclonal antibodies (UCHT1) directed against the antigen receptor/CD3 complex or the addition of the mitogens concanavalin A or phytohemagglutinin to human T lymphoblasts induced an elevation of the cytosolic free calcium concentration ([Ca2+]i) as monitored by the fluorescence of the intracellular fura-2. The rise in [Ca2+]i induced by these agents was effectively inhibited by staurosporine, an agent which inhibits protein kinase (PK)C and PKA. Conversely the PKC activator 12-O-tetradecanoyl phorbol-13-acetate decreased the delay and accelerated the rate of elevation of [Ca2+]i induced by the mitogens and UCHT1. Increasing the concentration of cAMP or cGMP in the T lymphoblasts had no effect on agonist-induced elevation of [Ca2+]i. Our data indicate that PKC can exert a positive feedback on the level of cytosolic Ca2+ in T lymphocytes, in contrast to what has been observed with other cells.",

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T1 - Inhibition by staurosporine of mitogen-induced calcium mobilisation in human T lymphoblasts

AU - Ward, Stephen G.

AU - Cantrell, Doreen

AU - Westwick, John

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Y1 - 1988/11/7

N2 - Addition of monoclonal antibodies (UCHT1) directed against the antigen receptor/CD3 complex or the addition of the mitogens concanavalin A or phytohemagglutinin to human T lymphoblasts induced an elevation of the cytosolic free calcium concentration ([Ca2+]i) as monitored by the fluorescence of the intracellular fura-2. The rise in [Ca2+]i induced by these agents was effectively inhibited by staurosporine, an agent which inhibits protein kinase (PK)C and PKA. Conversely the PKC activator 12-O-tetradecanoyl phorbol-13-acetate decreased the delay and accelerated the rate of elevation of [Ca2+]i induced by the mitogens and UCHT1. Increasing the concentration of cAMP or cGMP in the T lymphoblasts had no effect on agonist-induced elevation of [Ca2+]i. Our data indicate that PKC can exert a positive feedback on the level of cytosolic Ca2+ in T lymphocytes, in contrast to what has been observed with other cells.

AB - Addition of monoclonal antibodies (UCHT1) directed against the antigen receptor/CD3 complex or the addition of the mitogens concanavalin A or phytohemagglutinin to human T lymphoblasts induced an elevation of the cytosolic free calcium concentration ([Ca2+]i) as monitored by the fluorescence of the intracellular fura-2. The rise in [Ca2+]i induced by these agents was effectively inhibited by staurosporine, an agent which inhibits protein kinase (PK)C and PKA. Conversely the PKC activator 12-O-tetradecanoyl phorbol-13-acetate decreased the delay and accelerated the rate of elevation of [Ca2+]i induced by the mitogens and UCHT1. Increasing the concentration of cAMP or cGMP in the T lymphoblasts had no effect on agonist-induced elevation of [Ca2+]i. Our data indicate that PKC can exert a positive feedback on the level of cytosolic Ca2+ in T lymphocytes, in contrast to what has been observed with other cells.

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KW - Fura-2

KW - Staurosporine

KW - T lymphocyte

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ER -

Inhibition by staurosporine of mitogen-induced calcium mobilisation in human T lymphoblasts

Abstract

Keywords

ASJC Scopus subject areas

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