(C) Working model: MSR1 is activated by ligation through many different substrates, including apoptotic cells, fucoidan or oxidised LDL (Signal 1). However, only when the macrophage is IL-4-activated (Signal 2) becomes MSR1 ubiquitylated by an unknown E2/E3 ligase. This ubiquitylation recruits Tab2/3, Tak1, Mkk7 and finally JNK, thereby allowing MSR1 to signal directly through the JNK signalling pathway which induces pro-inflammatory gene transcription. 