Receptorinteracting

Receptorinteracting is a term used in cell biology to describe proteins or protein interactions that occur at or with cell surface receptors to relay signals inside the cell. In practice, it most often refers to the receptor-interacting protein (RIP) family, a group of kinases and scaffolding proteins that participate in signaling pathways initiated by tumor necrosis factor (TNF) receptors, Toll-like receptors, NOD-like receptors, and other receptor systems.

Members of the RIP family include RIPK1, RIPK2, and RIPK3 in vertebrates. They differ in domain organization: RIPK1 and RIPK3 carry kinase domains and RHIM motifs that enable assembly of signaling complexes, with RIPK1 also containing a death domain. RIPK2 features a CARD domain and principally links NOD1/NOD2 sensing to downstream NF-κB and MAP kinase activation. These proteins can act as scaffolds to promote survival signaling or, under certain conditions, contribute to cell death pathways such as apoptosis or necroptosis, depending on ubiquitination, phosphorylation, and interaction partners.

Functionally, receptor-interacting proteins participate in coordinating inflammatory and immune responses. In TNF receptor 1 signaling, RIPK1 helps form signaling complexes that drive NF-κB and MAPK activation for cell survival, while altered regulation can shift signaling toward apoptosis or necroptosis via RIPK3 and MLKL. RIPK2 transduces signals from intracellular receptors to promote inflammatory gene expression. The outcomes are highly context-dependent, affected by cellular state, post-translational modifications, and the presence of other signaling regulators.

Clinical relevance is noted in inflammatory and degenerative diseases where dysregulated receptor-interacting signaling contributes to pathology. Targeting RIP kinases, particularly RIPK1, has been explored as a therapeutic strategy for inflammatory diseases, ischemia-reperfusion injury, and sepsis, highlighting the importance of receptor-interacting pathways in health and disease.