Hematopoietin Receptors

Cytokines of the hematopoietic system interact with their receptors to stimulate production of functional blood cells from pluripotential, multipotent, and lineage-committed progenitors/precursors. The hematopoietin or cytokine receptor superfamily is characterized by single-span membrane proteins without enzymatic activity in cytoplasmic domains. Although some receptor subfamilies are dimers of a single unique receptor subunit, such as the erythropoietin receptor, most subfamilies consist of a multisubunit complex with a unique and specific ligand-binding subunit and a common shared signaling subunit. Binding of specific ligands to extracellular domains results in conformational changes and activation of members of the Janus kinase (JAK) family, which bind to receptor cytoplasmic domains. This results in receptor tyrosine phosphorylation and initiates a downstream signaling cascade that involves activation of signal transducers including signal transducer and activator of transcription (STAT), Ras, mitogen-activated protein kinases, PI 3-kinase, and Akt. These receptors signal a number of functions important in hematopoiesis including stimulation of proliferation, commitment to specific lineage, differentiation/maturation, protection from apoptosis, and functional activation of mature cells.