Catecholamine activation of p38 MAPK in S49 T lymphosarcoma cells is dependent on Protein Kinase A

Abstract

The catecholamine norepinephrine (NE) functions through a β2AR/cAMP/PKA pathway in T cells leading to altered immune function. p38 MAPK is an important intracellular signaling mediator for environmental stressors and plays a role in cell survival, apoptosis, and inflammation. To determine a relationship between NE‐mediated immune dysfunction and the p38 MAPK pathway, S49 wild type cells were incubated in the presence and absence of NE or a cAMP analogue, and the levels of activated (dually phosphophorylated, pTpY180/182) p38 MAPK were detected by ELISA. Activated p38 MAPK increased upon NE or cAMP treatment within 5 min and was sustained for 30 min. When the cells were treated with nadolol, a β2AR antagonist, the activation of p38 MAPK by NE was inhibited. Treatment of an S49 PKA mutant cell line (kin‐) with NE or cAMP, unlike wt, showed no change in activated p38 MAPK levels. These results suggest that NE can signal through the β2AR/cAMP/PKA pathway to activate p38 MAPK and reveal a new signaling pathway for engagement of p38 MAPK through a G protein‐coupled receptor/PKA dependent mechanism. Supported by NIH.