[5] In contrast to M-CSF and G-CSF which are lineage specific, GM-CSF and its receptor play a role in earlier stages of development.

The receptor is primarily located on neutrophils, eosinophils and monocytes/macrophages, it is also on CD34+ progenitor cells (myeloblasts) and precursors for erythroid and megakaryocytic lineages, but only in the beginning of their development.

Surrounding sequences provide binding sites for several regulatory transcription factors similar to those for α chain (GATA, C/EBP, NF-κB).

In the membrane distant part are typically cysteine residues forming disulphide bonds, proline pair, which devies the extracellular domain into two fibronectin type III-like subdomains in seven stranded β-barrel structure.

Remaining extracellular domain acts as a soluble GM-CSFRα and have been identified in bone marrow, monocytes and macrophages, placenta and chorio-carcinoma cells.

[6][12] β subunit can be found in two distinct isoforms: classical full-length protein and alternative form with deletions in transmembrane domain.

Deletions results in truncated peptide with 23 original amino acids in the membrane proximal cytoplasmic region and 23 new ones in C-terminal tail.

[8] Activated kinases then phosphorylate tyrosine residues on cytoplasmic domain of β subunit, thus creating docking sites for Src homology 2 (SH2) domain-containing signalling proteins like Shc and STATs.

Soluble GM-CSFRα then clutches free ligands with similar affinity as membrane receptor and prevents binding of GM-CSF to the cell surface.

For example in quiescent hematopoietic stem cells the β chain is expressed at very low levels and the amount increases along initial differentiation of erythroid, megakaryocytic, granulocytic and monocytic lineages.

[6][11] Kinetics of the receptor in immature and mature myeloid cells in response to GM-CSF is readily regulated by internalization or just by above mentioned degradation and desensitization of β subunit (mainly in the earlier hematopoietic development).