HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 52, 52188-52194, December 26, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/52/52188    most recent M310656200v2 M310656200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shivakrupa, R. Articles by Swarup, G. Search for Related Content PubMed PubMed Citation Articles by Shivakrupa, R. Articles by Swarup, G. Social Bookmarking                      What's this?

Physical and Functional Interaction between Hck Tyrosine Kinase and Guanine Nucleotide Exchange Factor C3G Results in Apoptosis, Which Is Independent of C3G Catalytic Domain^*

R. Shivakrupa, Vegesna Radha, Ch. Sudhakar, and Ghanshyam Swarup¶

From the Centre for Cellular and Molecular Biology, Hyderabad 500 007, India

The hematopoietic cell kinase Hck is a Src family tyrosine kinase expressed in cells of myelomonocytic lineage, B lymphocytes, and embryonic stem cells. To study its role in signaling pathways we used the Hck-SH3 domain in protein interaction cloning and identified C3G, the guanine nucleotide exchange factor for Rap1 and R-Ras, as a protein that associated with Hck. This interaction was direct and was mediated partly through the proline-rich region of C3G. C3G could be co-immunoprecipitated with Hck from Cos-1 cells transfected with Hck and C3G. C3G was phosphorylated on tyrosine 504 in cells when coexpressed with Hck but not with a catalytically inactive mutant of Hck. Phosphorylation of endogenous C3G at Tyr-504 was increased by treatment of human myelomonocytic THP-1 cells with mercuric chloride, which is known to activate Hck tyrosine kinase specifically. Coexpression of Hck with C3G induced a high level of apoptosis in many cell lines by 30–02 h of transfection. Induction of apoptosis was not dependent on Tyr-504 phosphorylation or the catalytic domain of C3G but required the catalytic activity of Hck. Using dominant negative constructs of caspases we found that caspase-1, -8, and -9 are involved in this apoptotic pathway. These results suggest that C3G and Hck interact physically and functionally in vivo to activate kinase-dependent and caspase-mediated apoptosis, which is independent of catalytic domain of C3G.

Received for publication, September 26, 2003

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by a Senior Research Fellowship from the Council of Scientific and Industrial Research, India. Present address: Rm. 208, Bldg. 567, Leukocyte Biology Laboratory, National Cancer Institute, National Institutes of Health, Frederick, MD 21701.

Both authors have made equal contributions to this work.

^¶ To whom correspondence should be addressed. Tel.: 91-40-27160222; Fax: 91-40-27160311; E-mail: gshyam{at}ccmb.res.in.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. L. Chalasani, V. Radha, V. Gupta, N. Agarwal, D. Balasubramanian, and G. Swarup A Glaucoma-Associated Mutant of Optineurin Selectively Induces Death of Retinal Ganglion Cells Which Is Inhibited by Antioxidants Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1607 - 1614. [Abstract] [Full Text] [PDF]

				H.-R. Zhou, Q. Jia, and J. J. Pestka Ribotoxic Stress Response to the Trichothecene Deoxynivalenol in the Macrophage Involves the Src Family Kinase Hck Toxicol. Sci., June 1, 2005; 85(2): 916 - 926. [Abstract] [Full Text] [PDF]