Reactome | PKC-delta phosphorylates CARD9

PKC-delta phosphorylates CARD9

Stable Identifier

R-HSA-5607740

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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Activation of NF-kB signaling is a critical event downstream of CLEC7A (Dectin-1), CLEC6A (Dectin-2) (Bi et al. 2010) and CLEC4E (Mincle) (Yamasaki et al. 2008), requiring the adapter protein Caspase recruitment domain (CARD)-containing protein 9 (CARD9) in dendritic cells and in macrophages (Gross et al. 2006, Hara et al. 2007). CARD9 is analogous to CARD-containing MAGUK protein 1 (CARMA1), which mediates T-cell receptor (TCR) activation of NF-kB in lymphocytes. CARD9 is downstream of SYK and becomes phosphorylated by PRKCD (Protein kinase C-delta) phosphorylates CARD9 on Thr-231 (T231), which is required for the signal-induced association of CARD9 with B-cell lymphoma 10 (BCL10) and Mucosa-associated lymphoid tissue 1 (MALT1) and the subsequent recruitment of MAP3K transforming growth factor beta activated kinase 1 (TAK1), leading to activation of the NF-kB pathway (Strasser et al. 2012). A homozygous loss-of-function mutation in human CARD9 results in a premature termination codon (Gln295*). Patients with this mutation are highly susceptible to fungal infections (Glocker et al. 2009).

Literature References

PubMed ID	Title	Journal	Year
22265677	Syk kinase-coupled C-type lectin receptors engage protein kinase C-? to elicit Card9 adaptor-mediated innate immunity Baier, G, Rojowska, A, Ruland, J, Leitges, M, Neumann, K, Urlaub, H, Guler, R, Marakalala, MJ, Strasser, D, Hopfner, KP, Bergmann, H, Brown, GD, Brombacher, F	Immunity	2012