|Budget Amount *help
¥6,800,000 (Direct Cost : ¥6,800,000)
Fiscal Year 1994 : ¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1993 : ¥4,400,000 (Direct Cost : ¥4,400,000)
Receptor and cytoplasmic tyrosine kinases essential functions in the hematopoietic cell development and signal transduction. In this project, we have characterized novel receptor tyrosine kinases, STK and TIE which are expresed in hematopoietic cells.
STK encodes a 1,378 amino acid protein. STK was expressed in a various stage of hematopoietic cells including cells, but ont apparent expression in other adult tissues. We recently confirmed that STK prtein was phosphorylated by the binding of macrophage stimulating factor (MSP) of HGF-like protein (HLP) . As is the case in HGF/c-MET system, MSP/STK system is functional in hematopoietic cells. We have shown that MSP/STK play a role in the differentiation of macrophages and erythroid cells.
TIE is unclassified RTK which is expressed in megakaryocytes and stem cells as well as endothelial cells. The amino acid homology between murine TIE and TEK was 46.2% in total. They shared a unique structural prperty of coexistent immunoglobulin-like doma
in, epidermal growth factor-like repeats, and fibronectin type lll repeats in their extracellular domains. The mouse TIE and TEK genes are located very close in chromosome4. This is syntenic to human chromosome region, 1p34 and 9p21, where the human TIE and TEK gene are mapped, respectively. Thus, TIE and TEK are tow linked members of a gene. Flow cytomery shows that TIE is mainly expressed in the fraction of CD34-positive of c-kit-positive cells. lt is interesting that TIE and TEK are expressed in both endothelial cells and hematopoietic stem cells, since both cells are thought to originate from the same progenitor cells. We hope that characterization of these kinases will be helpful to elucidate the molecular mechanism of the growth regulation of hematopoietic stem cells.