MARK, a Novel Family of Protein Kinases That Phosphorylate Microtubule-Associated Proteins and Trigger Microtubule Disruption

MARK phosphorylates the microtubule-associated proteins tau, MAP2, and MAP4 on their microtubule-binding domain, causing their dissociation from microtubules and increased microtubule dynamics. We describe the molecular cloning, distribution, activation mechanism, and overexpression of two MARK prot...

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Bibliographic Details
Published in:Cell 1997-04, Vol.89 (2), p.297-308
Main Authors: Drewes, Gerard, Ebneth, Andreas, Preuss, Ute, Mandelkow, Eva-Maria, Mandelkow, Eckhard
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Caenorhabditis elegans
CHO Cells
Cloning, Molecular
Cricetinae
DNA, Complementary - genetics
Gene Expression
Humans
Microtubules - metabolism
Molecular Sequence Data
Molecular Weight
Organ Specificity
Peptide Fragments - genetics
Phosphorylation
Phylogeny
Protein-Serine-Threonine Kinases - chemistry
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - isolation & purification
Protein-Serine-Threonine Kinases - metabolism
Rats
Recombinant Fusion Proteins - metabolism
RNA, Messenger - analysis
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Substrate Specificity
Swine
tau Proteins - metabolism
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Summary:MARK phosphorylates the microtubule-associated proteins tau, MAP2, and MAP4 on their microtubule-binding domain, causing their dissociation from microtubules and increased microtubule dynamics. We describe the molecular cloning, distribution, activation mechanism, and overexpression of two MARK proteins from rat that arise from distinct genes. They encode Ser/Thr kinases of 88 and 81 kDa, respectively, and show similarity to the yeast kin1 + and C. elegans par-1 genes that are involved in the establishment of cell polarity. Expression of both isoforms is ubiquitous, and homologous genes are present in humans. Catalytic activity depends on phosphorylation of two residues in subdomain VIII. Overexpression of MARK in cells leads to hyperphosphorylation of MAPs on KXGS motifs and to disruption of the microtubule array, resulting in morphological changes and cell death.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(00)80208-1