DIFFERENTIAL ACTIVATION OF EXTRACELLULAR SIGNAL-REGULATED KINASE (ERK)1, ERK2, P38, AND C-JUN NH2-TERMINAL KINASE MITOGEN-ACTIVATED PROTEIN-KINASES BY BACTERIAL PEPTIDOGLYCAN

Soluble staphylococcal peptidoglycan (sPGN) is an inducer of cytokine secretion and may activate macrophages through the CD14 lipopolysaccha ride (LPS) receptor. To elucidate sPGN-activated signal transduction p athways, stimulation of mitogen-activated protein (MAP) kinases by sPG N was studied in mouse RAW264.7 macrophages. sPGN strongly activated e xtracellular signal-regulated kinase (ERK) 1 and ERK2, moderately acti vated cJun NH2 terminal kinase (JNK), and weakly activated p38 MAP kin ase, in contrast to LPS, which strongly activated all of these kinases , and phorbol 12,13-dibutyrate (PDB), which strongly activated ERK1 an d ERK2 but did not activate p38 or JNK. sPGN- and LPS-induced activati on of ERK1 and ERK2, unlike PDB-induced activation, was sensitive to i nhibition by herbimycin A and insensitive to inhibition by increased i ntracellular cAMP. These results demonstrate differential activation o f MAP kinases by sPGN, similar but not identical activation of signal transduction pathways by sPGN and LPS, and different mechanisms of MAP kinase activation by bacterial stimulants and phorbol esters.