Receptor Interacting Protein Kinases

Receptor Interacting Protein (RIP) kinases are characterized by a homologous kinase domain, but have distinct non-kinase regions, which are key to the specific function of each RIP kinase. They have key roles in various biological processes, including innate immunity, inflammation and regulation of cell death.

Products
Background
Literature (1)
Gene Data

Inhibitors

Cat. No. Product Name / Activity
6480 GSK 583
Potent RIPK2 inhibitor; orally bioavailable and cell permeable
6492 GSK'872
Potent and selective RIP3 kinase inhibitor
2324 Necrostatin-1
RIP1 kinase inhibitor; inhibits necroptosis
6598 OD 36 hydrochloride
Potent RIP2 kinase inhibitor

Related Targets

Receptor Interacting Protein (RIP) kinases are characterized by a homologous kinase domain, but have distinct non-kinase regions, which are key to the specific function of each RIP kinase. They have key roles in various biological processes, including innate immunity, inflammation and regulation of cell death.

RIP1-5 all have a N-terminal kinase domain. In addition to the kinase domain RIP1 contains an intermediate domain and a C-terminal death domain (DD), which binds to death receptors, such as TNF-R1, and adaptor proteins, such as TNF-receptor-associated death domain (TRADD). RIP1 is also able to bind to other kinases including RIP3. RIP2 also contains an intermediate domain, but has a C-terminal caspase activation and recruitment domain (CARD). RIP3 contains the N-terminal but lacks the intermediate domain and has a C-terminal sequence containing a RHIM (RIP homotypic interaction motif), also found in the intermediate domain of RIP1. Both RIP4 and 5 have C-terminal ankyrin domains.

RIP1 is widely expressed and along with RIP3 is an important mediator of regulated cell death. Following activation of death receptors, including TNF-R1, Fas and TNF-related apoptosis inducing ligand (TRAIL), a complex (complex I) comprising the TNFR-associated death protein (TRADD), TRAF2, cellular inhibitor of apoptosis (cIAP) and RIP1 is formed. This activates NF-κB, which promotes the expression of antiapoptotic proteins. Deubiquination of RIP1 enables its release from complex I and formation of a complex with Fas-associated death domain (FADD) and procaspase 8, known as complex II. Complex II promotes activation of procaspase 8 which triggers a caspase cascade culminating in apoptosis. However, if the caspases remain inactive, RIP1 forms a complex with RIP3, known as the necrosome, and necroptosis ensues. Thus, RIP1 is important in controlling the switch between inflammation and apoptosis.

RIP2 is an important mediator of the innate immune response. When bacterial peptides activate the cytosolic receptors NOD1 and NOD2, the CARD domain of RIP2 interacts with the CARD domain of NOD1/2, activating NF-κB and triggering the expression of inflammatory and antibacterial proteins, as well as autophagy. The functions of RIP4, 5 and 6 are less well understood; RIP4 has been shown to activate NF-κB and has a role in keratinocyte differentiation and cutaneous inflammation, while overexpression of RIP5 has been shown to drive cell apoptosis, but its physiological role is yet to be determined. RIP6 (LRRK1) is associated with the pathogenesis of Parkinson's disease.

Literature for Receptor Interacting Protein Kinases

Tocris offers the following scientific literature for Receptor Interacting Protein Kinases to showcase our products. We invite you to request* or download your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


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New Product Guide [Spring/Summer 2019]

Our new product guide highlights over 215 new products added to the Tocris Bioscience range during the first half of 2019.

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Receptor Interacting Protein Kinase Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
RIPK1 Human RIPK1 NM_003804 Q13546
Mouse Ripk1 NM_009068 Q60855
Rat Ripk1 NM_053599 NP_001100820
RIPK2 Human RIPK2 NM_003821 O43353
Mouse Ripk2 NM_138952 P58801
Rat Ripk2 NM_001191865 NP_001178794
RIPK3 Human RIPK3 NM_006871 Q9Y572
Mouse Ripk3 NM_019955 Q9QZL0
Rat Ripk3 NM_139342 NP_647558
RIPK4 Human RIPK4 NM_020639 P57078
Mouse Ripk4 XM_011246154 Q9ERK0
Rat Ripk4 NM_001107103 NP_001100573
RIPK5 Human DSTYK NM_015375 Q6XUX3
Mouse Dstyk NM_172516 Q6XUX1
Rat Dstyk NM_199463 NP_955750
RIPK6 Human LRRK1 NM_024652 Q38SD2
Mouse Lrrk1 NM_146191 Q3UHC2
Rat Lrrk1 NM_199463 NP_955750