The janus kinases (JAK) and signal transducers and activators of the transcription (STAT) pathway have been shown to be activated by a number of cytokines or growth factors and to play significant roles in the differentiation of various cell types. In the present study, we investigated the distribution of the JAK-STAT pathway using immunohistochemistry in the human epidermis. Each element of the pathway showed abundant and differential expression in the epidermis. The differential distribution of the elements was most strikingly observed in the horny keratinised cell and granular layers of the epidermis. JAK2, JAK3, STAT1 and STAT5 were expressed in high amounts, and JAK1, TYK2, STAT2, STAT3, STAT4 and STAT6 to a much lesser extent in the horny cell layer. JAK3, TYK2, STAT2, STAT3, STAT4 and STAT6 were more abundantly expressed in the granular layer than the lower layers of the epidermis. JAK1, STAT1 and STAT5 were expressed at almost the same levels in the various layers of the epidermis. These results show that elements of the JAK-STAT pathway are abundantly and differentially expressed in the epidermis. It is suggested that each element of the pathway may play a role at a distinct stage of keratinocyte differentiation.Key words : Skin ; keratinocyte differentiation.
The janus kinases (JAK) and signal transducers and activators of the transcription (STAT) signalling pathway have been shown to be activated by a number of cytokines, growth factors, and oncogenic tyrosine kinases (Ihle, 1995). JAKs associate with the intracellular domains of particular receptors and become activated by ligand binding to the receptors at the cell surface. Activated JAKs consecutively phosphorylate STATs at distinct tyrosine residues. The tyrosine-phosphorylated STATs leave the receptor complex, translocate to the nucleus, and promote the transcriptional activation of ligand-inducible genes (Darnell, 1997). To date, 4 members of the JAK family (JAK1, JAK2, JAK3 and TYK2) and 7 of the STAT family (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6) have been identifiedCorrespondence to Dr Koichi Suzuki, Department of Legal Medicine, Osaka Medical College, 2-7 Daigaku, Takatsuki, 569-8686, Japan. Tel. : j81 726 831221 ; fax : j81 726 846515 ; e-mail : leg010!art.osaka-med.ac.jp (Ihle, 1995). The pathway has been demonstrated to play significant roles in determining differentiation processes of a variety of cell types, including myeloid leukaemia cells Nakajima et al. 1996 ;Yamanaka et al. 1996), murine mammary epithelial cells (Liu et al. 1997), helper T cells (Shimoda et al. 1996Takeda et al. 1996), murine haematopoietic cells (Rane & Reddy, 1994) and rat hepatocytes (Runge et al. 1998).The epidermis provides a useful model for investigating the differentiation process. In the epidermis, the outer (horny cell) layers of terminally differentiated cells are repopulated from a basal layer of proliferating keratinocytes. The proliferating keratinocytes are released from the substratum, migrate outwards and enter a...