MAP/microtubule affinity-regulating kinase 4

Definition:

Serine/threonine-protein kinase. Phosphorylates the microtubule-associated protein MAPT/TAU. Also phosphorylates the microtubule-associated proteins MAP2 and MAP4. Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles. Required for the initiation of axoneme extension during cilium assembly. Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro. Plays a role in cell cycle progression, specifically in the G1/S checkpoint. Reduces neuronal cell survival. Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation.

References:

[1]. Gucci Jijuan Gu, et al. Role of individual MARK isoforms in phosphorylation of tau at Ser²⁶² in Alzheimer's disease. Neuromolecular Med. 2013 Sep;15(3):458-69. [Content Brief]

[2]. Stefanie Kuhns, et al. The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis. J Cell Biol. 2013 Feb 18;200(4):505-22. [Content Brief]

[3]. Armin Schneider, et al. Identification of regulated genes during permanent focal cerebral ischaemia: characterization of the protein kinase 9b5/MARKL1/MARK4. J Neurochem. 2004 Mar;88(5):1114-26. [Content Brief]

[4]. Li Li, et al. Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) is a negative regulator of the mammalian target of rapamycin complex 1 (mTORC1). J Biol Chem. 2013 Jan 4;288(1):703-8. [Content Brief]

[5]. Davide Rovina, et al. Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) plays a role in cell cycle progression and cytoskeletal dynamics. Eur J Cell Biol. 2014 Aug-Sep;93(8-9):355-65. [Content Brief]

[6]. Bernhard Trinczek, et al. MARK4 is a novel microtubule-associated proteins/microtubule affinity-regulating kinase that binds to the cellular microtubule network and to centrosomes. J Biol Chem. 2004 Feb 13;279(7):5915-23. [Content Brief]

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