GM-CSF ELISA Kit, Rat

The GM-CSF receptor is a heterodimer that comprises a major binding subunit (GMRalpha) and a major signaling subunit (betac). GM-CSF receptor activation follows general rules observed for other class I cytokine receptors that invoke receptor dimerization and tyrosine transphosphorylation of cytoplasmic domains. The GM-CSF receptor does not have intrinsic tyrosine kinase activity, but associates with the tyrosine kinase Jak2 that is required for betac transphosphorylation and the initiation of signaling and biological activity. The cytoplasmic domains of both GMRalpha and betac are essential for receptor activation, but only betac associates with Jak2. GM-CSF receptor activation is initiated by the low-affinity interaction of GM-CSF with GMRalpha chain to form a binary complex. Recruitment of the binary complex to preformed betac dimers generates a 2:2:2 hexameric complex and converts GM-CSF binding to high affinity. Oligomerization of the hexamer complex generates a higher order dodecamer complex that is required for receptor tyrosine phosphorylation in trans by associated Jak2 and initiates intracellular signal transduction. Importantly, the biochemical effects of GM-CSF signaling at different concentrations have been determined and have also been shown to be separable. Low pM concentrations of GM-CSF mediate betac Ser585 phosphorylation, leading to 14-3-3 binding, PI-3 kinase activation, and hemopoietic cell survival, whereas at concentrations of 10 pM or more, GM-CSF mediates betac Tyr577 phosphorylation, Shc recruitment, and PI-3 kinase activation, thereby promoting both survival and proliferation. Biochemically, Ser585 and Tyr577 phosphorylation are mutually exclusive (Ser585 phosphorylation is extinguished as Tyr phosphorylation comes on) and unidirectional (Ser585 phosphorylation occurs first as GM-CSF concentrations are increased).³ In addition, GM-CSF signaling also regulates the activity of Bcl-2 family members.⁴