Cat. No.
MABL-2607
Application
crystallize, neutralize
Isotype
Engineer antibody
Species Reactivity
Human
Clone No.
23-57-137-1
From
Recombinant Antibody
Specificity
The anitbody binds to human PTHrP (The KD ~ 0.1 nM) at a site closely overlapping with the GPCR parathyroid hormone receptor 1 binding site - the epitope is between residues 20 and 30, with some contribution from residues 15-20 (aa 14-34 are important for receptor binding and aa1-34 are important for full signal tranduction). PTHrP is known to be a causative factor of humoural hypercalcemia of malignancy (HHM), which is frequently found at advanced stages of cancer. The protein binds to PTHR1, which is expressed on the surface of cells of the osteoblast lineage and of the kidney tubule; this interaction actively promotes bone resorption, in a manner identical to that of PTH.
Alternative Names
PTHrP; PTH-rP; Parathyroid hormone-like protein; PLP; PTHrP[1-34]
UniProt
P12272
Immunogen
The anti-PTHrP antibody was prepared by immunizing mice with synthetic human bovine thyroglobulin-conjugated PTHrP (aa 1-34) and generating the hybridoma cell line #23-57-137-1
Application Notes
The antibody blocks the binding of PTHrP to parathyroid hormone receptor 1 through binding to a site closely overlapping with the receptor-interacting site at the extracellular loop and juxtamembrane regions. The antibody does not block the action of parathyroid hormone (PTH) through the same receptor. The antibody inhibits the action of PTHrP-(1–34) in promoting cAMP production by osteosarcoma cells by 90%,. The antibody also functions in vivo, and can treat nude mice rendered hypercalcemic by PAN-7-JCK cells, and prevents cachexia in mice bearing the LC6-JCK human lung cancer xenograft, independent of the calcium-lowering effect of the antibody. The fab fragment of this antibody, generated by papain digestion, has been used for cystallization of PTHrP at atomic level resolution.
Antibody First Published
McKinstry et al. Structural basis for antibody discrimination between two hormones that recognize the parathyroid hormone receptor. J Biol Chem. 2009 Jun 5;284(23):15557-63. PMID:19346515
Note on publication
Describes the creation of a neutralizing mAb against human PTHrP. The in vitro and in vivo activity of the mAb was studied and a crsytal structure of the fab fragment complexed with PTHrP (aa 1-108) was generated.
Size
100 μg Purified antibody.
Concentration
1 mg/ml.
Purification
Protein A affinity purified
Buffer
PBS with 0.02% Proclin 300.
Storage Recommendation
Store at 4⁰C for up to 3 months. For longer storage, aliquot and store at - 20⁰C.
