- Synonyms:
- Par1
- MARK
- Par1/MARK is a serine/threonine kinase.
- Par1 was first identified in C. elegans through genetic screens for polarity regulators and was later recognized as the mammalian kinase, MARK (Microtubule Affinity-Regulating Kinase), which phosphorylates microtubule-associated proteins like tau to regulate microtubule stability.
- Par1 is evolutionarily conserved and is referred to as MARK in mammals. Four homologs of Par1 exist in mammals: MARK1 (Par1a), MARK2 (Par1b), MARK3 (Par1c), and MARK4 (Par1d).
- It plays a fundamental role in cell polarity, cytoskeletal organization, and microtubule regulation.
- These kinases regulate cell shape, epithelial junctions, and neuronal differentiation by phosphorylating microtubule-associated proteins (MAPs) such as tau, MAP2, and MAP4, leading to microtubule destabilization.
- Par1/MARK kinases are particularly important in epithelial cell polarity, where they localize to the lateral membrane and help establish apicobasal polarity by interacting with Par3/Par6/aPKC complexes. Their proper function ensures correct cell division orientation and tissue organization.
- They are important for neuronal differentiation, particularly in axon-dendrite specification and neuronal migration.
- Dysregulation of Par1 activity is associated with various diseases, including cancer and neurodegenerative disorders like Alzheimer’s disease, where excessive phosphorylation of tau by MARK kinases contributes to neurofibrillary tangles.
- Abbreviations:
- Par1 (Partitioning Defective 1)
- MARK (Microtubule Affinity-Regulating Kinase)
