The ERK cascade, a new pathway involved in the activation of store-mediated calcium entry in human platelets.

Store-mediated Ca(2+) entry (SMCE) is the main pathway for Ca(2+) influx in platelets and other nonexcitable cells, yet how depletion of the intracellular Ca(2+) stores leads to the activation of Ca(2+) entry across the plasma membrane remains unclear. Recent work in platelets favors a secretionlike conformational coupling mechanism involving the Ca(2+)-permeable channel protein, Trp1, in the plasma membrane and the type-II inositol 1,4,5-trisphosphate receptor in the membrane of the Ca(2+) store, which is located in the endoplasmic reticulum. Extracellular signal-regulated kinases (ERKs) are common participants in a broad variety of signal transduction pathways in human platelets, and inactivation of the ERK cascade has been shown to reduce Ca(2+) entry stimulated by thapsigargin or thrombin. The role of ERK in SMCE into human platelets was found to be independent of the cytoskeleton and a downstream effector of the small guanosine-triphosphate-binding protein Ras.