CSF2RB Research Reagents

CSF2RB Background

Colony-stimulating factor 2 receptor subunit beta (CSF2RB), a shared common beta chain of the high-affinity receptor for human granulocyte-macrophage colony-stimulating factor (GMCSF), interleukin 3 (IL-3), and interleukin 5 (IL-5) ^[1], is a member of the type I cytokine family of the receptors. So it is also called cytokine receptor common subunit beta. CSF2RB does not bind any cytokine by itself but converts the ligand‐bound alpha subunit (CSF2RA) to a high-affinity state for GM‐CSF, IL‐3, and IL‐5, it is therefore important for signal transduction ^[2][3]. CSF2RA is primarily a ligand-binding subunit with a short 54-amino acid intracellular domain that exhibits specificity for signaling. Cross‐competition of binding between these cytokines occurs by competition for the common beta subunit between different alpha subunits in the human ^[1]. Although CSF2RB lacks intrinsic kinase activity, the tyrosine phosphorylation of CSF2RB triggers the occurrence of multiple signaling pathways. The membrane-proximal region of CSF2RB contains a conserved proline‐rich motif termed box 1 and serves as a binding site for JAK2 ^[4]. Upon ligand binding and receptor oligomerization, JAK2 kinase is activated due to JAK2 transphosphorylation ^[4]. JAK2 phosphorylation of CSF2RB or other cytoplasmic signaling proteins is important to transmit signals from the cell surface to the nucleus. Phosphorylation of tyrosines on CSF2RB allows recruitment and subsequent activation of SH2 (src‐homology) and PTB (phosphotyrosine binding) domain proteins, ultimately resulting in the initiation of numerous downstream signaling cascades such as JAK/STAT pathway, the Ras/MAP kinase pathway, and the PI3K pathway ^[5][6][7]. These processes promote survival, proliferation, and differentiation. Defects in CSF2RB cause congenital pulmonary alveolar proteinosis (PAP), an autosomal recessive fatal respiratory disease.

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[3] Bagley CJ, Woodcock JM, et al. The structural and functional basis of cytokine receptor activation: lessons from the common β subunit of the granulocyte‐macrophage colony‐stimulating factor, interleukin‐3 (IL‐3) and IL‐5 receptors [J]. Blood 1997; 89: 1471-1482.
[4] Quelle FW, Sato N, et al. JAK2 associates with the βC chain of the receptor for granulocyte‐macrophage colony‐stimulating factor, and its activation requires the membrane proximal region. Mol Cell Biol 1994; 14: 4335-4341.
[5] Mark A. Guthridge Frank C. Stomski, et al. Mechanism of Activation of the GM‐CSF, IL‐3, and IL‐5 Family of Receptors [J]. Volume16, Issue5, September 1998, Pages 301-313.
[6] Sato N, Sakamaki K, et al. Signal transduction by the high affinity GM‐CSF receptor: two distinct cytoplasmic regions of the common β subunit responsible for different signaling [J]. EMBO J 1993; 12: 4181-4189.
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