PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and regulates actin cytoskeletal organization

Citation
Tm. Moore et al., PSK, a novel STE20-like kinase derived from prostatic carcinoma that activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and regulates actin cytoskeletal organization, J BIOL CHEM, 275(6), 2000, pp. 4311-4322
Citations number
77
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
275
Issue
6
Year of publication
2000
Pages
4311 - 4322
Database
ISI
SICI code
0021-9258(20000211)275:6<4311:PANSKD>2.0.ZU;2-2
Abstract
Degenerate polymerase chain reaction against conserved kinase catalytic sub domains identified 15 tyrosine and serine-threonine kinases expressed in su rgically removed prostatic carcinoma tissues, including six receptor kinase s (PDGFBR, IGF1-R, VEGFR2, MET, RYK, and EPH-A1), six non-receptor kinases (ABL, JAK1, JAK2, TYK2, PLK-1, and EMK), and three novel kinases, Several o f these kinases are oncogenic, and may function in the development of prost ate cancer. One of the novel kinases is a new member of the sterile 20 (STE 20) family of serine-threonine kinases which we have called prostate-derive d STE20-like kinase (PSK) and characterized functionally. PSK encodes an op en reading frame of 3705 nucleotides and contains an N-terminal:kinase doma in. Immunoprecipitated PSK phosphorylates myelin basic protein and transfec ted PSK stimulates MKK4 and MKK7 and activates the c-Jun N-terminal kinase mitogen-activated protein kinase pathway. Microinjection of PSK into cells results in localization of PSK to a vesicular compartment and causes a mark ed reduction in actin stress fibers, In contrast, C-terminally truncated PS K (1-349) did not localize to this compartment or induce a decrease in stre ss fibers demonstrating a requirement for the C terminus. Kinase-defective PSK (K57A) was unable to reduce stress fibers. PSK is the first member of t he STE20 family lacking a Cdc42/Rac binding domain that has been shown to r egulate both the c-Jun N-terminal kinase mitogen-activated protein kinase p athway and the actin cytoskeleton.