NALP2 (also known as PAN1/PYPAF2) is a member of the NLR (NACHT-LRR) family which includes both NODs and NALPs (Bruey et al, 2004). Alternative names for the NLR family include CATERPILLER, NOD and NOD-LRR. NLR family members are thought to be intracellular pathogen-recognition receptors (PRRs) (reviewed in Martionon and Tschopp, 2005 and 2007; Creagh and O'Neill, 2006; Petrilli et al, 2005). PRRs are key components of immune systems and are involved in innate effector mechanisms and activation of adaptive immunity. Toll-like receptors (TLRs) are the most well studied PPRs and overlaps have been identified between the signaling pathways used by some NLRs and TLRs suggesting redundancy and cooperation between NLR and TLR pathways. At least fourteen NALPs have been identified in the human genome, and a common feature among NALPs 1-3, 6, and 12 is their ability to to recruit the adaptor protein ASC through a homotypic PYD-PYD interaction, which in turn recruits caspase-1 through a CARD-CARD interaction. The oligomerization of NALPs is thought to bring the inflammatory caspases into close proximity leading to their activation within the inflammasome. The inflammasome is a multiprotein complex of more than 700kD that is responsible for the activation of caspases 1 and 5, which leads to the processing and secretion of the pro-inflammatory cytokines IL-1b and IL-18. The NALP2/3 inflammasomes contain, in addition to NALP2 or NALP3, the caspase recruitment domain (CARD)-containing protein Cardinal, ASC and caspase 1. Processing of the pro-inflammatory cytokines IL-1b and IL-18 by caspases leads to to the secretion of active cytokines and elicits a potent inflammatory response. Similar to TLRs, activation of the inflammasome by NLRs occurs through the recognition of pathogen-associated molecular patterns (PAMPs) through their LRR (leucine rich) domains): TLR family members recognize bacteria, viruses, fungi and protoza, whereas NLRs with known functions recognize bacteria. The expression of NALP2 is upregulated in THP-1 macrophage cells by LPS and certain cytokines including interferon g and b, supporting a role for NALP2 in host-defense and inflammation (Bruey et al, 2004). Additionally, NALP2 is expressed in several human tumor cell lines. However, the endogenous expression of NALP2 varies widely among tumor cells lines, with the highest levels found in MCF-7 and MDA-MB-435 breast cancer, Caco2 colon cancer and UACC62 melanoma cells (Bruey et al, 2004). Recognizes NALP2; human NALP2 is a 1062aa protein. Is specific for NALP2 does not cross-react with related family members PAN2 or NAC.
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