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Molecular and Cellular Biology, March 2003, p. 2068-2082, Vol. 23, No. 6
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.6.2068-2082.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The STE20 Kinase HGK Is Broadly Expressed in Human Tumor Cells and Can Modulate Cellular Transformation, Invasion, and Adhesion

Jocelyn H. Wright,* Xueyan Wang, Gerard Manning, Brandon J. LaMere, Phuong Le, Shirley Zhu, Deepak Khatry, Peter M. Flanagan, Sharon D. Buckley, David B. Whyte, Anthony R. Howlett, James R. Bischoff, Kenneth E. Lipson, and Bahija Jallal

Sugen, Inc., South San Francisco, California 94080

Received 15 July 2002/ Returned for modification 17 September 2002/ Accepted 6 November 2002

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-RasV12-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.

* Corresponding author. Mailing address: Sugen, Inc., South San Francisco, CA 94080. Phone: (650) 837 3477. Fax: (650) 837 3313. E-mail: jocelyn-wright{at}sugen.com.

Molecular and Cellular Biology, March 2003, p. 2068-2082, Vol. 23, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.6.2068-2082.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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