Interaction of Hic-5, A Senescence-related Protein, with Focal Adhesion Kinase*
- Hiroo Fujita‡§,
- Kenjiro Kamiguchi‡§,
- Donny Cho‡,
- Motoko Shibanuma¶,
- Chikao Morimoto‡,‖ and
- Kouichi Tachibana‡**
- From the ‡Department of Cancer Immunology & AIDS, Dana-Faber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, the ¶Department of Microbiology, Showa University School of Pharmaceutical Sciences, 1-5-8, Shinagawa-ku, Tokyo, Japan, and the ‖Department of Clinical Immunology and AIDS Research Center, Institute of Medical Science, University of Tokyo, 4-6-1, Shiroganedai, Minato-ku, Tokyo, Japan
Abstract
Hydrogen peroxide-inducible clone (Hic)-5 is induced during the senescent process in human fibroblasts, and the overexpression of Hic-5 induces a senescence-like phenotype. Structurally, Hic-5 and paxillin, a 68-kDa cytoskeletal protein, share homology such as the LD motifs in the N-terminal half and the LIM domains in the C-terminal half. Here we show that Hic-5 binds to focal adhesion kinase (FAK) by its N-terminal domain, and is localized to focal adhesions by its C-terminal LIM domains. However, Hic-5 is not tyrosine phosphorylated either by the coexpressed FAK in COS cells or by integrin stimulation in 293T cells. Furthermore, overexpression of Hic-5 results in a decreased tyrosine phosphorylation of paxillin. These findings suggest that putative functions of Hic-5 are the recruitment of FAK to focal adhesions and a competitive inhibition of tyrosine phosphorylation of paxillin.
Footnotes
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↵* This work was supported by National Institutes of Health Grants AR33713 and AI29530.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ Contributed equally to the results of this study.
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↵** To whom correspondence and reprint requests should be addressed: Dept. of Cancer Immunology & AIDS, Dana-Faber Cancer Institute, 44 Binney St., Boston, MA 02115. Tel.: 617-632-4484; Fax: 617-632-4569; E-mail: tachiban{at}mbcrr.harvard.edu.
- FAK
- focal adhesion kinase
- hic-5
- hydrogen peroxide-inducible clone-5
- SH
- Src homology
- anti-Tyr(P)
- anti-phosphotyrosine
- mAb
- monoclonal antibody
- pAb
- polyclonal antibody
- FN
- fibronectin
- HA
- hemagglutinin
- GST
- glutathione S-transferase
- EGFP
- enhanced green fluorescent protein
- CT
- C-terminal domain
- MAP kinase
- mitogen-activated protein kinase
- p130Cas
- Crk-associated substrate.
- Received March 31, 1998.
- Revision received July 9, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
