FIG. 7.

Mechanisms of cytosolic kinase activation following macrophage stimulation with LPS or infection with Salmonella: a working model. LPS and Salmonella stimulate the MEK/ERK module by a common mechanism, involving activation of one or more herbimycin-sensitive tyrosine kinases (Tyr-K) and of PI 3-K. PI 3-K stimulates MEK/ERK via activation of PLD and of DAG-sensitive PKC (DAG-s PKC). Activation of PI 3-K, PLD, and PKC by LPS has been demonstrated previously (19, 28, 32). The nature of the intermediates laying between PKC and MEK is unknown. This scheme represents the working hypothesis that we currently favor. Alternative models are possible and are discussed in the text. Solid arrows, steps in the pathway for which experimental evidence is provided in the paper; dashed arrows, speculative steps in the pathway.