RIPK2
RIPK2 (receptor-interacting serine/threonine-protein kinase 2, also known as RICK, RIP2, CARDIAK and CARD3) is a CARD-containing kinase that acts as a key effector of NOD1 and NOD2 signalling. It links bacterial peptidoglycan sensing to NF-kappa-B activation in innate and adaptive immunity. Browse Assay Genie's current range of RIPK2 research reagents below, or read on for the biology behind the target.
RIPK2 is a serine/threonine/tyrosine-protein kinase that plays an essential role in modulating innate and adaptive immune responses. It is a key effector of the NOD1 and NOD2 pathways. When bacterial peptidoglycans activate NOD1 and NOD2, the receptors oligomerise and recruit RIPK2 through CARD-CARD interactions, which leads to the formation of RIPK2 filaments. Recruited RIPK2 autophosphorylates and is polyubiquitinated. The E3 ligases XIAP, BIRC2 and BIRC3 add 'Lys-63'-linked chains, and the LUBAC complex adds 'Met-1'-linked (linear) chains. RIPK2 then acts as a scaffold for downstream effectors.
The 'Met-1'-linked chains recruit IKBKG/NEMO, while the 'Lys-63'-linked chains act as docking sites for TAB2 and TAB3. These bring MAP3K7/TAK1 to IKBKG/NEMO and activate IKBKB/IKKB. NF-kappa-B is then released from its inhibitors and moves into the nucleus, where it drives transcription of genes involved in immune response, growth control and protection against apoptosis. The kinase activity itself is dispensable for NOD1 and NOD2 signalling. RIPK2 also contributes to NOD2-driven NF-kappa-B activation by promoting Src-mediated tyrosine phosphorylation of ARHGEF2. In adaptive immunity, it promotes BCL10 phosphorylation and NF-kappa-B activation after T-cell receptor engagement. It also has a role in RHOA inactivation downstream of NGFR signalling.
The RIPK2 gene encodes a member of the receptor-interacting protein (RIP) family and belongs to the TKL Ser/Thr protein kinase family. The protein has a C-terminal caspase activation and recruitment domain (CARD). It is a potent activator of NF-kappaB and an inducer of apoptosis in response to various stimuli. UniProt lists it in the cytoplasm, cell membrane and endoplasmic reticulum. The mouse ortholog is Ripk2.
RIPK2 is a key effector downstream of NOD1 and NOD2, which sense bacterial peptidoglycans, so it is central to studies of innate immune activation.
Ubiquitin-dependent scaffolding by RIPK2 recruits NEMO and TAK1 and activates IKKB, making it a focus for dissecting NF-kappa-B signal transduction.
RIPK2 promotes BCL10 phosphorylation and NF-kappa-B activation after TCR engagement, linking it to adaptive immune responses.
XIAP, BIRC2, BIRC3 and LUBAC modify RIPK2, and the protein can induce apoptosis, so it is relevant to ubiquitin signalling and cell-fate research.
RIPK2 is recruited by activated NOD1 and NOD2 through CARD-CARD interactions. It is then ubiquitinated and serves as a scaffold that recruits NEMO, TAB2, TAB3 and TAK1, leading to IKKB and NF-kappa-B activation. It also contributes to T-cell receptor signalling through BCL10.
RIPK2 is also known as RICK, RIP2, CARDIAK and CARD3. HGNC lists its full name as receptor interacting serine/threonine kinase 2, previously receptor-interacting serine-threonine kinase 2. It belongs to the RIP kinase family and the CARD-containing gene group.
According to UniProt, the protein kinase activity of RIPK2 is dispensable for NOD1 and NOD2 signalling. Its scaffolding role, based on ubiquitin chains, is what drives downstream signalling. The mouse ortholog is Ripk2; check the datasheet of any product for its validated reactivity.
Other receptor-interacting protein kinases involved in NF-kappa-B signalling, inflammation and cell death.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O43353; product specifications from Assay Genie datasheets.