Phosphorylation of MAP2c and MAP4 by MARK kinases leads to the destabilization of microtubules in cells.
Microtubules serve as transport tracks in molecular mechanisms governing cellular shape and polarity. Rapid transitions between stable and dynamic microtubules are regulated by several factors, including microtubule-associated proteins (MAPs). We have shown that MAP/microtubule affinity regulating kinases (MARK) can phosphorylate the microtubule-associated-proteins MAP4, MAP2c, and tau on their microtubule-binding domain in vitro. This leads to their detachment from microtubules (MT) and an increased dynamic instability of MT. Here we show that MARK protein kinases phosphorylate MAP2 and MAP4 on their microtubule-binding domain in transfected CHO cells. In CHO cells expressing MARK1 or MARK2 under control of an inducible promoter, MARK2 phosphorylates an endogenous MAP4-related protein. Prolonged expression of MARK2 results in microtubule-disruption, detachment of cells from the substratum, and cell death. Concomitant with microtubule disruption, we also observed a breakdown of the vimentin network, whereas actin fibers remained unaffected. Thus, MARK seems to play an important role in controlling cytoskeletal dynamics.
Ebneth
A
A
Max-Planck Unit for Structural Molecular Biology, Hamburg, Germany.
Drewes
G
G
Mandelkow
E M
EM
Mandelkow
E
E
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002455:Cell Division; D006224:Cricetinae; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D007382:Intermediate Filaments / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D000199:Actins; D018985:Epitopes, B-Lymphocyte; C489788:MAP2 protein, human; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D016875:tau Proteins; C105549:MARK2 protein, rat; C484552:Mark1 protein, rat; D017346:Protein Serine-Threonine Kinases