Phosphorylation regulates the microtubule-destabilizing activity of stathmin and its interaction with tubulin.
Stathmin is a regulator of microtubule dynamics which undergoes extensive phosphorylation during the cell cycle as well as in response to various extracellular factors. Four serine residues are targets for protein kinases: Ser-25 and Ser-38 for proline-directed kinases such as mitogen-activated protein kinase and cyclin-dependent protein kinase, and Ser-16 and Ser-63 for cAMP-dependent protein kinase. We studied the effect of phosphorylation on the microtubule-destabilizing activity of stathmin and on its interaction with tubulin in vitro. We show that triple phosphorylation on Ser-16, Ser-25, and Ser-38 efficiently inhibits its activity and prevents its binding to tubulin.
Di Paolo
G
G
Institut de Biologie Cellulaire et de Morphologie, University of Lausanne, Switzerland.
Antonsson
B
B
Kassel
D
D
Riederer
B M
BM
Grenningloh
G
G
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000648:ultrastructure; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002453:Cell Cycle; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008868:Microtubule Proteins; D008870:Microtubules / Q000502:physiology* / Q000648:ultrastructure; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine; D011392:Proline; D011494:Protein Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine; D050777:Stathmin; D013552:Swine; D014404:Tubulin / Q000378:metabolism*
D003432:Cross-Linking Reagents; D008868:Microtubule Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; C493995:STMN1 protein, human; D050777:Stathmin; D014404:Tubulin; D010768:Phosphoserine; D012694:Serine; D011392:Proline; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018844:Cyclin-Dependent Kinases