Systemin, an 18-amino-acid polypeptide released from wound sites on tomato leaves caused by insects or other mechanical damage, systemically regulates the activation of over 20 defensive genes in tomato plants in response to herbivore and pathogen attacks. Systemin is processed from a larger prohormone protein, called prosystemin, by proteolytic cleavages. However, prosystemin lacks a signal sequence and glycosylation sites and is apparently not synthesized through the secretory pathway, but in the cytoplasm. The polypeptide activates a lipid-based signal transduction pathway in which the 18:3 fatty acid, linolenic acid, is released from plant membranes and converted to the oxylipin signaling molecule jasmonic acid. A wound-inducible systemin cell surface receptor with an M(r) of 160,000 has recently been identified. The receptor regulates an intracellular cascade including, depolarization of the plasma membrane, the opening of ion channels, an increase in intracellular Ca(2+), activation of a MAP kinase activity and a phospholipase A(2) activity. These rapid changes appear to play important roles leading to the intracellular release of linolenic acid from membranes and its subsequent conversion to jasmonic acid, a potent activator of defense gene transcription. Although the mechanisms for systemin processing, release, and transport are still unclear, studies of the timing of the synthesis and of the intracellular localization of wound- and systemin-inducible mRNAs and proteins indicates that differential syntheses of signal pathway genes and defensive genes are occurring in different cell types. This signaling cascade in plants exhibits extraordinary analogies with the signaling cascade for the inflammatory response in animals.