※ Jak family introduction

    Jak (Janus kinase) are tyrosine protein kinase. Four members have been found in human genome, known as Jak1-3 and TYK2. TYK2 was the first screened from a T-cell library using low stringency hydridization techniques. Jak1-3 were subsequently cloned. Human Jak1, Jak2 and TYK2 localize on chromosomes 1p13.3, 9p24 and 19p13.2. Jak3 was further mapped to human chromosome 19p131. Jaks contain several JAK homology regions (JH1-JH7). Two kinase domains have been found in Jaks. The C-terminal kinase domain (JH1) posses the catalytic ability and another domain is likely to be catalytic inactive. The N-terminal domain of Jaks often mediates the interaction with cytokine/interferon/growth hormone receptors. The Jaks is original being inactive state and recruited to several receptors and subsequently get activated via auto-phosphorylation or phosphorylation by others Jaks. Activated Jaks will mediate the phosphorylation and activation Signal Transducers and Activators of Transcription (STAT) which will translocate to nucleus and regulate the gene expression. In addition, Jaks also mediate the recruitment of other molecules involved in signal transduction including src-family kinases, protein tyrosine phosphatases, MAP kinases, PI3 kinase. These molecules will also result in the activation of transcription factors and gene expression (1).

Reference
1. Rane, S.G. and Reddy, E.P. (2000) Janus kinases: components of multiple signaling pathways . Oncogene, 19, 5662-5679. PMID: 11114747