Receptor tyrosine kinases and the regulation of hematopoiesis.

The ongoing production of mature blood cells during the lifetime of an animal is vital for survival. Hematopoiesis is the complex process whereby a small population of pluripotential stem cells give rise to mature cell types with specialized functions. The development of mature blood cells proceeds in a hierarchical fashion originating from a self-renewable stem cell population that gradually becomes committed to lineage-restricted differentiation. Two major themes concerning the regulation of hematopoiesis have emerged. First, the proliferation, survival and differentiation of immature progenitor cells depends on extracellular signals produced by cells within the hematopoietic microenvironment. Second, protein tyrosine phosphorylation is the major biochemical mechanism by which the extracellular signals are transmitted and interpreted. In this review we will concentrate on the role of receptors with intrinsic tyrosine kinase activity (RTKs) in hematopoietic regulation. RTKs form part of a highly conserved signaling mechanism that plays an important role in the development of evolutionary diverse organisms. During hematopoiesis, RTKs are a central component of the mechanism by which hematopoietic stem cells receive extracellular signals and interpret these signals to direct the lineage restricted differentiation of multipotential progenitors. In addition, RTKs may also play an important regulatory role in the ontogeny of the hematopoietic system during embryonic and fetal development. Taken together, RTKs are an important component of the mechanisms that regulate the development and behavior of hematopoietic stem cells.