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Differential requirement for p56lck in HIV-tat versus TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal kinase, and apoptosis.
J Immunol. 2000 May 15; 164(10):5156-66.JI

Abstract

HIV-tat protein, like TNF, activates a wide variety of cellular responses, including NF-kappa B, AP-1, c-Jun N-terminal kinase (JNK), and apoptosis. Whether HIV-tat transduces these signals through the same mechanism as TNF is not known. In the present study we investigated the role of the T cell-specific tyrosine kinase p56lck in HIV-tat and TNF-mediated cellular responses by comparing the responses of Jurkat T cells with JCaM1 cells, an isogeneic lck-deficient T cell line. Treatment with HIV-tat protein activated NF-kappa B, degraded I kappa B alpha, and induced NF-kappa B-dependent reporter gene expression in a time-dependent manner in Jurkat cells but not in JCaM1 cells, suggesting the critical role of p56lck kinase. These effects were specific to HIV-tat, as activation of NF-kappa B by PMA, LPS, H2O2, and TNF was minimally affected. p56lck was also found to be required for HIV-tat-induced but not TNF-induced AP-1 activation. Similarly, HIV-tat activated the protein kinases JNK and mitogen-activated protein kinase kinase in Jurkat cells but not in JCaM1 cells. HIV-tat also induced cytotoxicity, activated caspases, and reactive oxygen intermediates in Jurkat cells, but not in JCaM1 cells. HIV-tat activated p56lck activity in Jurkat cells. Moreover, the reconstitution of JCaM1 cells with p56lck tyrosine kinase reversed the HIV-tat-induced NF-kappa B activation and cytotoxicity. Overall, our results demonstrate that p56lck plays a critical role in the activation of NF-kappa B, AP-1, JNK, and apoptosis by HIV-tat protein but has minimal or no role in activation of these responses by TNF.

Authors+Show Affiliations

Cytokine Research Section, Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10799874

Citation

Manna, S K., and B B. Aggarwal. "Differential Requirement for P56lck in HIV-tat Versus TNF-induced Cellular Responses: Effects On NF-kappa B, Activator Protein-1, c-Jun N-terminal Kinase, and Apoptosis." Journal of Immunology (Baltimore, Md. : 1950), vol. 164, no. 10, 2000, pp. 5156-66.
Manna SK, Aggarwal BB. Differential requirement for p56lck in HIV-tat versus TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal kinase, and apoptosis. J Immunol. 2000;164(10):5156-66.
Manna, S. K., & Aggarwal, B. B. (2000). Differential requirement for p56lck in HIV-tat versus TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal kinase, and apoptosis. Journal of Immunology (Baltimore, Md. : 1950), 164(10), 5156-66.
Manna SK, Aggarwal BB. Differential Requirement for P56lck in HIV-tat Versus TNF-induced Cellular Responses: Effects On NF-kappa B, Activator Protein-1, c-Jun N-terminal Kinase, and Apoptosis. J Immunol. 2000 May 15;164(10):5156-66. PubMed PMID: 10799874.
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TY - JOUR T1 - Differential requirement for p56lck in HIV-tat versus TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal kinase, and apoptosis. AU - Manna,S K, AU - Aggarwal,B B, PY - 2000/5/9/pubmed PY - 2000/6/10/medline PY - 2000/5/9/entrez SP - 5156 EP - 66 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 164 IS - 10 N2 - HIV-tat protein, like TNF, activates a wide variety of cellular responses, including NF-kappa B, AP-1, c-Jun N-terminal kinase (JNK), and apoptosis. Whether HIV-tat transduces these signals through the same mechanism as TNF is not known. In the present study we investigated the role of the T cell-specific tyrosine kinase p56lck in HIV-tat and TNF-mediated cellular responses by comparing the responses of Jurkat T cells with JCaM1 cells, an isogeneic lck-deficient T cell line. Treatment with HIV-tat protein activated NF-kappa B, degraded I kappa B alpha, and induced NF-kappa B-dependent reporter gene expression in a time-dependent manner in Jurkat cells but not in JCaM1 cells, suggesting the critical role of p56lck kinase. These effects were specific to HIV-tat, as activation of NF-kappa B by PMA, LPS, H2O2, and TNF was minimally affected. p56lck was also found to be required for HIV-tat-induced but not TNF-induced AP-1 activation. Similarly, HIV-tat activated the protein kinases JNK and mitogen-activated protein kinase kinase in Jurkat cells but not in JCaM1 cells. HIV-tat also induced cytotoxicity, activated caspases, and reactive oxygen intermediates in Jurkat cells, but not in JCaM1 cells. HIV-tat activated p56lck activity in Jurkat cells. Moreover, the reconstitution of JCaM1 cells with p56lck tyrosine kinase reversed the HIV-tat-induced NF-kappa B activation and cytotoxicity. Overall, our results demonstrate that p56lck plays a critical role in the activation of NF-kappa B, AP-1, JNK, and apoptosis by HIV-tat protein but has minimal or no role in activation of these responses by TNF. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10799874/Differential_requirement_for_p56lck_in_HIV_tat_versus_TNF_induced_cellular_responses:_effects_on_NF_kappa_B_activator_protein_1_c_Jun_N_terminal_kinase_and_apoptosis_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10799874 DB - PRIME DP - Unbound Medicine ER -