A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus.

In eukaryotic cells, the accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers a signaling pathway from the ER to the nucleus. Several yeast mutants defective in this pathway map to the ERN1 gene, which protects cells from lethal consequences of stress by signaling for increased expression of BiP and other ER proteins. ERN1 encodes a 1115 amino acid transmembrane protein (Ern1p) whose glycosylated N-terminal portion is located inside microsomes and whose cytoplasmic C-terminal portion carries an essential protein kinase activity. We postulate that Ern1p is the proximal sensor of events in the ER and that binding of ligand causes transduction of information across the ER membrane, leading to activation of a specific set of transcription factors.