title: The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion.
abstract: HGK (hepatocyte progenitor kinase-like/germinal center kinase-like kinase) is a member of the human STE20/mitogen-activated protein kinase kinase kinase kinase family of serine/threonine kinases and is the ortholog of mouse NIK (Nck-interacting kinase). We have cloned a novel splice variant of HGK from a human tumor line and have further identified a complex family of HGK splice variants. We showed HGK to be highly expressed in most tumor cell lines relative to normal tissue. An active role for this kinase in transformation was suggested by an inhibition of H-Ras(V12)-induced focus formation by expression of inactive, dominant-negative mutants of HGK in both fibroblast and epithelial cell lines. Expression of an inactive mutant of HGK also inhibited the anchorage-independent growth of cells yet had no effect on proliferation in monolayer culture. Expression of HGK mutants modulated integrin receptor expression and had a striking effect on hepatocyte growth factor-stimulated epithelial cell invasion. Together, these results suggest an important role for HGK in cell transformation and invasiveness.
authors.affiliation: Sugen, Inc., South San Francisco, California 94080, USA. jocelyn-wright@sugen.com
authors.forename: Jocelyn H
authors.initials: JH
authors.lastname: Wright
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wang
authors.forename: Gerard
authors.initials: G
authors.lastname: Manning
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: LaMere
authors.forename: Phuong
authors.initials: P
authors.lastname: Le
authors.forename: Shirley
authors.initials: S
authors.lastname: Zhu
authors.forename: Deepak
authors.initials: D
authors.lastname: Khatry
authors.forename: Peter M
authors.initials: PM
authors.lastname: Flanagan
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Buckley
authors.forename: David B
authors.initials: DB
authors.lastname: Whyte
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Howlett
authors.forename: James R
authors.initials: JR
authors.lastname: Bischoff
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Lipson
authors.forename: Bahija
authors.initials: B
authors.lastname: Jallal
mesh_terms: D016475:3T3 Cells; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D003001:Cloning, Molecular; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D005799:Genes, Dominant; D005909:Glioblastoma / Q000201:enzymology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D020935:MAP Kinase Signaling System; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured / Q000201:enzymology
chemical_list: D016023:Integrins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017228:Hepatocyte Growth Factor; C117090:MAP4K4 protein, human; D017346:Protein Serine-Threonine Kinases