Alpha-protein kinase 1

Definition:

Serine/threonine-protein kinase that detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) and initiates an innate immune response, a critical step for pathogen elimination and engagement of adaptive immunity. Specifically recognizes and binds ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria. ADP-Heptose-binding stimulates its kinase activity to phosphorylate and activate TIFA, triggering pro-inflammatory NF-kappa-B signaling. May be involved in monosodium urate monohydrate (MSU)-induced inflammation by mediating phosphorylation of unconventional myosin MYO9A. May also play a role in apical protein transport by mediating phosphorylation of unconventional myosin MYO1A. May play a role in ciliogenesis.

References:

[1]. Martin Heine, et al. Alpha-kinase 1, a new component in apical protein transport. J Biol Chem. 2005 Jul 8;280(27):25637-43. [Content Brief]

[2]. Chi-Pin Lee, et al. ALPK1 phosphorylates myosin IIA modulating TNF-α trafficking in gout flares. Sci Rep. 2016 May 12;6:25740. [Content Brief]

[3]. Ping Zhou, et al. Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose. Nature. 2018 Sep;561(7721):122-126. [Content Brief]

[4]. Milica Milivojevic, et al. ALPK1 controls TIFA/TRAF6-dependent innate immunity against heptose-1,7-bisphosphate of gram-negative bacteria. PLoS Pathog. 2017 Feb 21;13(2):e1006224. [Content Brief]

[5]. Stephanie Zimmermann, et al. ALPK1- and TIFA-Dependent Innate Immune Response Triggered by the Helicobacter pylori Type IV Secretion System. Cell Rep. 2017 Sep 5;20(10):2384-2395. [Content Brief]

[6]. Lloyd B Williams, et al. ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder. Genet Med. 2019 Sep;21(9):2103-2115. [Content Brief]

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