The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion

被引：109

作者：

Wright, JH ^{[1
]}

Wang, XY ^{[1
]}

Manning, G ^{[1
]}

LaMere, BJ ^{[1
]}

Le, P ^{[1
]}

Zhu, S ^{[1
]}

Khatry, D ^{[1
]}

Flanagan, PM ^{[1
]}

Buckley, SD ^{[1
]}

Whyte, DB ^{[1
]}

Howlett, AR ^{[1
]}

Bischoff, JR ^{[1
]}

Lipson, KE ^{[1
]}

Jallal, B ^{[1
]}

机构：

[1] Sugen Inc, San Francisco, CA 94080 USA

来源：

MOLECULAR AND CELLULAR BIOLOGY | 2003年 / 23卷 / 06期

关键词：

D O I：

10.1128/MCB.23.6.2068-2082.2003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2068 / 2082

页数：15

共 54 条

[1] PAK to the future [J].