GM-CSFR α Protein

Dipeptidyl peptidase 4 (DPPIV, also known as CD26) is an approximately 110 kDa serine exopeptidase that releases Xaa-Pro or Xaa-Ala dipeptides from the N-terminus of oligo- and polypeptides. Mature human DPPIV consists of a 6 amino acid (aa) cytoplasmic tail, a 22 aa transmembrane segment, and a 738 aa extracellular domain (ECD) that contains the catalytic active site. DPPIV is expressed as a noncovalent homodimer on the surface of epithelial cells, endothelial cells, and activated lymphocytes, and it can be released by MMP mediated shedding. It regulates immune and endocrine function through the cleavage of multiple chemokines, growth factors, and peptide hormones. CD26/dipeptidyl peptidase (DPP) 4 is a membrane-bound protein found in many cell types of the body, and a soluble form is present in body fluids. There is longstanding evidence that various primary tumors and also metastases express CD26/DPP4 to a variable extent. By cleaving dipeptides from peptides with a proline or alanine in the penultimate position at the N-terminus, it regulates the activity of incretin hormones, chemokines and many other peptides. Due to these effects and interactions with other molecules, a tumor promoting or suppressing role can be attributed to CD26/DPP4. DPPIV plays a major role in glucose metabolism. It is responsible for the degradation of incretins such as GLP-1. DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum increased in some neoplasms and decreased in others. DPPIV also binds the enzyme adenosine deaminase specifically and with high affinity. The significance of this interaction has yet to be established.GM-CSF receptor alpha is a member of the cytokine family of receptors. GM-CSF receptor alpha is found in the pseudoautosomal region of the X and Y chromosomes. GM-CSF receptor alpha has different isoform, with some of the isoforms being membrane-bound and others being soluble. Soluble GM-CSF receptor alpha subunit is a soluble isoform of the GMR alpha that is believed to arise exclusively through alternative splicing of the GMR alpha gene product. The sGMR alpha mRNA is expressed in a variety of tissues, but it is not clear which cells are capable of secreting the protein. Hereditary pulmonary alveolar proteinosis (hPAP) is a rare disorder of pulmonary surfactant accumulation and hypoxemic respiratory failure caused by mutations in GM-CSF receptor alpha, which results in reduced GM-CSF-dependent pulmonary surfactant clearance by alveolar macrophages. While no pharmacologic therapy currently exists for hPAP, it was recently demonstrated that endotracheal instillation of wild-type or gene-corrected mononuclear phagocytes results in a significant and durable therapeutic efficacy in a validated murine model of hPAP.