title: v-Src-dependent down-regulation of the Ste20-like kinase SLK by casein kinase II.
abstract: We have previously shown that the Ste20-like kinase SLK is a microtubule-associated protein inducing actin stress fiber disassembly. Here, we show that v-Src expression can down-regulate SLK activity. This down-regulation is independent of focal adhesion kinase but requires v-Src kinase activity and membrane translocation. SLK down-regulation by v-Src is indirect and is accompanied by SLK hyperphosphorylation on serine residues. Deletion analysis revealed that casein kinase II (CK2) sites at position 347/348 are critical for v-Src-dependent modulation of SLK activity. Further studies show that CK2 can directly phosphorylate SLK at these positions and that inhibition of CK2 in v-Src-transformed cells results in normal kinase activity. Finally, CK2 and SLK can be co-localized in fibroblasts spreading on fibronectin-coated substrates, suggesting a mechanism whereby SLK may be regulated at sites of actin remodeling, such as membrane lamellipodia and ruffles, through CK2.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H8L6, Canada.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Chaar
authors.forename: Paul
authors.initials: P
authors.lastname: O'reilly
authors.forename: Irwin
authors.initials: I
authors.lastname: Gelman
authors.forename: Luc A
authors.initials: LA
authors.lastname: Sabourin
mesh_terms: D000818:Animals; D047390:Casein Kinase II / Q000502:physiology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003599:Cytoskeleton / Q000502:physiology; D015536:Down-Regulation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology; D006801:Humans; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021381:Protein Transport; D000099317:Hippo Kinases
chemical_list: D047390:Casein Kinase II; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D017346:Protein Serine-Threonine Kinases; C485733:SLK protein, human; D000099317:Hippo Kinases