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

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.