tailieunhanh - Báo cáo khoa học: TEC family kinases in health and disease – loss-of-function of BTK and ITK and the gain-of-function fusions ITK–SYK and BTK–SYK

The TEC family is ancient and constitutes the second largest family of cyto-plasmic tyrosine kinases. In 1993, loss-of-function mutations in theBTK gene were reported as the cause of X-linked agammaglobulinemia. Of all the existing 90 tyrosine kinases in humans, Bruton’s tyrosine kinase (BTK) is the kinase for which most mutations have been identified. | ịFEBS Journal MINIREVIEW TEC family kinases in health and disease - loss-of-function of BTK and ITK and the gain-of-function fusions ITK-SYK and BTK-SYK Alamdar Hussain1 2 Liang Yu1 3 Rani Faryal1 2 Dara K. Mohammad1 Abdalla J. Mohamed1 4 and C. I. Edvard Smith1 1 ClinicalResearch Center Department of Laboratory Medicine Karolinska Institutet Huddinge University Hospital Sweden 2 Department of Biosciences COMSATS Institute of Information Technology Islamabad Pakistan 3 Department of Hematology Huaian No. 1 Hospital Nanjing MedicalUniversity Huaian Jiangsu China 4 Faculty of Science Biology Universiti Brunei Darussalam Gadong Brunei Darussalam Keywords AkT BMX BTK ITK lymphocyte PH domain RLK TEC TXK X-linked agammaglobulinemia 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 These authors contributed equally to this work Received 31 August 2010 revised 21 March 2011 accepted 20 April 2011 doi The TEC family is ancient and constitutes the second largest family of cytoplasmic tyrosine kinases. In 1993 loss-of-function mutations in the BTK gene were reported as the cause of X-linked agammaglobulinemia. Of all the existing 90 tyrosine kinases in humans Bruton s tyrosine kinase BTK is the kinase for which most mutations have been identified. These experiments of nature collectively provide a form of mutation scanning with direct implications for the several hundred endogenous signaling proteins carrying domains also found in BTK. In 2009 an inactivating mutation in the ITK gene was shown to cause susceptibility to lethal Epstein-Barr virus infection. Both kinases represent interesting targets for inhibition in the case of BTK as an immunosuppressant whereas there is evidence that the inhibition of inducible T-cell kinase ITK could influence the infectivity of HIV and also have anti-inflammatory activity.