In addition to inducing new transcriptional activities that lead within a few hours to the accumulation of heat shock proteins (Hsps), heat shock activates within minutes the major signaling transduction pathways involving mitogen-activated protein kinases, extracellular signal–regulated kinase, stress-activated protein kinase 1 (SAPK1)–c-Jun N-terminal kinase, and SAPK2-p38. These kinases are involved in both survival and death pathways in response to other stresses and may, therefore, contribute significantly to the heat shock response. In the case of p38, the activation leads to the phosphorylation and activation of one of the Hsps, Hsp27. Phosphorylation occurs very early during stress, is tightly regulated, and results from the triggering of a highly specific heat shock–sensing pathway.