Open AccessControl of Microtubule Dynamics by Oncoprotein 18: Dissection of the Regulatory Role of Multisite Phosphorylation during Mitosis
Author(s) -
Niklas Larsson,
Ulrica Marklund,
Helena Melander Gradin,
Göran Brattsand,
Martin Gullberg
Publication year - 1997
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.17.9.5530
Subject(s) - stathmin , biology , phosphorylation , cyclin dependent kinase , mitosis , microbiology and biotechnology , microtubule , phosphorylation cascade , polo like kinase , protein phosphorylation , metaphase , spindle apparatus , kinase , tubulin , cell cycle , protein kinase a , biochemistry , cell division , gene , cell , chromosome
Oncoprotein 18 (Op18; also termed p19, 19K, metablastin, stathmin, and prosolin) is a conserved protein that regulates microtubule (MT) dynamics. Op18 is multisite phosphorylated on four Ser residues during mitosis; two of these Ser residues, Ser-25 and Ser-38, are targets for cyclin-dependent protein kinases (CDKs), and the other two Ser residues, Ser-16 and Ser-63, are targets for an unidentified protein kinase. Mutations of the two CDK sites have recently been shown to result in a mitotic block caused by destabilization of MTs. To understand the role of Op18 in regulation of MT dynamics during mitosis, in this study we dissected the functions of all four phosphorylation sites of Op18 by combining genetic, morphological, and biochemical analyses. The data show that all four phosphorylation sites are involved in switching off Op18 activity during mitosis, an event that appears to be essential for formation of the spindle during metaphase. However, the mechanisms by which specific sites down-regulate Op18 activity differ. Hence, dual phosphorylation on the CDK sites Ser-25 and Ser-38 appears to be required for phosphorylation of Ser-16 and Ser-63; however, by themselves, the CDK sites are of only minor importance in direct regulation of Op18 activity. Subsequent phosphorylation of either Ser-16, Ser-63, or both efficiently switches off Op18 activity.