GENOMIC STRUCTURE AND PROMOTER REGION OF THE MURINE JANUS-FAMILY TYROSINE KINASE, JAK3

Genomic DNA sequences encoding the murine Janus family tyrosine kinase Jak3 were isolated to determine the intron-exon structure of the gene and to investigate the phylogeny of Jak-family kinases. The murine Ja k3 gene comprises approximately 15 kbp of genomic DNA and consists of 23 exons. The organization of sequences encoding the pseudo-kinase dom ain of Jak3 is similar to the intron-exon structure encoding catalytic domains of Src-family tyrosine kinases, whereas the pattern of intron s-exons encoding the Jak3 kinase domain shows no structural similarity to that of other tyrosine kinase genes. Genomic analysis further indi cates that alternative splicing gives rise to different forms of the m urine Jak3 mRNA encoding different isoforms of the Jak3 protein. Analy sis of Jak3 intron-exon structure also suggests that a mutation in the human JAK3 gene responsible for a severe combined immune deficiency ( SCID) phenotype results from aberrant splicing of the JAK3 transcript. Finally, potential regulatory sequences in the upstream region of the murine Jak3 gene were analyzed and are discussed in relation to the k nown expression pattern of Jak3.