The RIP kinases: crucial integrators of cellular stress

Since the discovery of the first member ten years ago, the receptor-interacting protein (RIP) family kinases have emerged as essential sensors of cellular stress. The different members integrate both extracellular stress signals transmitted by various cell-surface receptors and signals emanating from intracellular stress. The cascades of events initiated by activated RIPs are complex. Not only are pro-survival, inflammatory and immune responses triggered by RIP kinases via the activation of transcription factors such as NF-kappaB and AP-1, but opposing, death-inducing programs can also be initiated by the RIP kinases. Hence, RIP kinases are crucial regulators of cell survival and cell death.