The Bmx Tyrosine Kinase: a Signal Mediator in Hematopoietic and Endothelial/epithelial Cells
Year: 2003
Type: dissertation
Abstract: Development and survival of a multicellular organism is dependent on cell-to-cell signaling. Cells must be able to communicate with each other and to respond to extracellular stimuli in an appropriate manner. Signaling between cells takes place either locally, as a result of a direct contact between cells, or via secreted soluble signal mediators, both locally acting growth factors and cytokines and systemically circulating endocrine hormones. For fat-soluble hormones like steroid hormones, the receptor molecule is usually an intracellular transcription factor. In contrast, soluble polypeptides, such as growth factors acting on solid tissues and cytokines, mainly involved in the survival and differentiation of hematopoietic cells, activate membrane anchored receptor molecules. These receptors initiate a cascade of covalent phosphorylations culminating in a change in gene transcription events. In multicellular organisms, phosphorylation, especially on tyrosine residues plays major roles in transducing signals from the plasma membrane to the cell nucleus. To date, over 90 protein tyrosine kinases have been identified in the human genome, out of which at least 32 encode intracellular tyrosine kinases (1). In this thesis work, one intracellular signal mediator, the Bmx tyrosine kinase, a member of the Tec gene subfamily, has been studied. The study was undertaken to identify the expression pattern of the gene as well as to elucidate the function and signaling properties of the protein in different cell types. We show that among nonhematopoietic cells, the Bmx gene is almost exclusively expressed in arterial endothelial cells, with only some expression in epithelial cells. This is the first example of an intracellular tyrosine kinase showing such restricted arterial expression. We also identify four receptors, two hematopoietically expressed cytokine receptors and two endothelial specific receptor tyrosine kinases that activate Bmx. In hematopoietic cells, Bmx regulates granulocytic differentiation of progenitor cells, while overexpression of Bmx in skin keratinocytes induces a phenotype characterized by proliferation and scaling of the skin and induction of inflammation and angiogenesis. However, mice lacking a functional Bmx gene do not show any noticeable phenotype, suggesting that members of the Tec family at least to some extent are redundant. The Bmx tyrosine kinase 9 REVIEW OF THE LITERATURE 1. THE DEVELOPMENT OF THE CIRCULATORY SYSTEM: COMMON ORIGINS OF ENDOTHELIAL AND HEMATOPOIETIC CELLS 1.1. Vasculogenesis and angiogenesis The blood circulation system is the first organ system to function during embryonic development. The circulatory system is necessary for distribution of oxygen and nutrients to, and removal of waste products from developing organs and tissues. The first step leading to the formation of the embryonic vasculature is the induction of the ventral-lateral mesoderm, which gives rise to cardiac, pronephric, hematopoietic and vascular endothelial tissues. The hematopoietic and vascular endothelial cell lineages are thought to be particularly closely related as hemangioblasts, which are aggregated into blood islands in the yolk sac, can differentiate into both endothelial cells and primitive hematopoietic cells (Figure 1, for reviews, see (2, 3)). In addition, differentiating hematopoietic and endothelial cells share several surface markers, such as CD31 and CD34 (4, 5).
Source: Työväentutkimus Vuosikirja
Author: Niklas Ekman
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2138810469