tailieunhanh - Báo cáo khoa học: NF-jB regulates the transcription of protein tyrosine kinase Tec

The tyrosine kinase expressed in hepatocellular carcinoma (Tec) is a non-receptor protein tyrosine kinase (PTK) that is expressed in hematopoietic cells, such as B and T lymphocytes, myeloid lineage cells and neutrophils. Mutations in the humanBtkgene cause X-linked agammaglobulinemia (XLA), but the corresponding mutation in mice results in a much milder defect. | NF-kB regulates the transcription of protein tyrosine kinase Tec Liang Yu1 2 Oscar E. Simonson1 Abdalla J. Mohamed1 and C. I. Edvard Smith1 1 Department of Laboratory Medicine ClinicalResearch Center Karolinska Institutet Karolinska University HospitalHuddinge Stockholm Sweden 2 Department of Hematology Huaian NO. 1 hospital Nanjing MedicalUniversity Huaian Jiangsu China Keywords Bortezomib hydrodynamic transfection NF-kB Tec transcription Correspondence L. Yu Department of Hematology Huaian No. 1 Hospital Nanjing MedicalUniversity Huaian 223300 Jiangsu China Fax 86 517 84907078 Tel 86 517 84952303 E-mail C. I. E. Smith Department of Laboratory Medicine Clinical Research Center Karolinska Institutet Karolinska University HospitalHuddinge SE-141 86 Stockholm Sweden Fax 46 8 58583650 Tel 46 8 58583651 E-mail Received 10 June 2009 revised 5 September 2009 accepted 16 September 2009 doi The tyrosine kinase expressed in hepatocellular carcinoma Tec is a nonreceptor protein tyrosine kinase PTK that is expressed in hematopoietic cells such as B and T lymphocytes myeloid lineage cells and neutrophils. Mutations in the human Btk gene cause X-linked agammaglobulinemia XLA but the corresponding mutation in mice results in a much milder defect. However the combined inactivation of Btk and Tec genes in mice cause a severe phenotype resembling XLA. Tec is involved in the regulation of both B and T lymphocytes fine-tuning of TCR BCR signaling and also activation of the nuclear factor of activated T cells. Previous work has shown that the transcription factors Sp1 and can bind and regulate the Tec promoter. In this study we demonstrate that NF-kB is an essential transcription factor for optimal expression of the Tec gene and identify a unique functionally active NF-kB binding site in its promoter. The NF-kB subunit p65 RelA directly induced transcriptional activity of the Tec promoter. Moreover we also found .