Parathyroid hormone-related protein

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Parathyroid hormone-like hormone
Protein PTHLH PDB 1bzg.png
PDB rendering based on 1bzg.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PTHLH ; BDE2; HHM; PLP; PTHR; PTHRP
External IDs OMIM168470 MGI97800 HomoloGene2113 GeneCards: PTHLH Gene
RNA expression pattern
PBB GE PTHLH 206300 s at tn.png
PBB GE PTHLH 211756 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5744 19227
Ensembl ENSG00000087494 ENSMUSG00000048776
UniProt P12272 n/a
RefSeq (mRNA) NM_002820 NM_008970
RefSeq (protein) NP_002811 NP_032996
Location (UCSC) Chr 12:
28.11 – 28.13 Mb
Chr 6:
147.25 – 147.26 Mb
PubMed search [1] [2]

Parathyroid hormone-related protein (or PTHrP) is a protein member of the parathyroid hormone family. It is occasionally secreted by cancer cells (breast cancer, certain types of lung cancer including squamous cell lung carcinoma). However, it also has normal functions.

Function[edit]

PTHrP acts as an endocrine, autocrine, paracrine, and intracrine hormone. It regulates endochondral bone development by maintaining the endochondral growth plate at a constant width. It also regulates epithelial-mesenchymal interactions during the formation of the mammary glands.

Tooth eruption[edit]

PTHrP is critical in the intraosseous phase of tooth eruption where it acts as a signalling molecule to stimulate local bone resorption. Without PTHrP, the bony crypt surrounding the tooth follicle will not resorb, and therefore the tooth will not erupt. In the context of tooth eruption, PTHrP is secreted by the cells of the Reduced Enamel Epithelium.

Mammary glands[edit]

It aids in normal mammary gland development.[1][2] It is necessary for maintenance of the mammary bud. Loss of PTHrP or its receptor causes the mammary bud cell fate to change back into epidermis. In lactation, it may regulate in conjunction with the calcium sensing receptor the mobilization and transfer of calcium to the milk, as well as placental transfer of calcium.

Humoral hypercalcemia of malignancy[edit]

PTHrP is related in function to the "normal" parathyroid hormone. When a tumor secretes PTHrP, this can lead to hypercalcemia.[3] As this is sometimes the first sign of the malignancy, hypercalcemia caused by PTHrP is considered a paraneoplastic phenomenon. PTHR1 is responsible for most cases of humoral hypercalcemia of malignancy.

PTHrP shares the same N-terminal end as parathyroid hormone and therefore it can bind to the same receptor, the Type I PTH receptor (PTHR1). PTHrP can simulate most of the actions of PTH including increases in bone resorption and distal tubular calcium reabsorption, and inhibition of proximal tubular phosphate transport.

However, PTHrP is less likely than PTH to stimulate 1,25-dihydroxyvitamin D production. Therefore, PTHrP does not increase intestinal calcium absorption.

Genetics[edit]

Four alternatively spliced transcript variants encoding two distinct isoforms have been observed. There is also evidence for alternative translation initiation from non-AUG (CUG and GUG) start sites, in-frame and downstream of the initiator AUG codon, to give rise to nuclear forms of this hormone.[4]

Discovery[edit]

The protein was first isolated in 1987 by T.J. Martin's team at the University of Melbourne. Miao et al. showed that disruption of the PTHrP gene in mice caused a lethal phenotype and distinct bone abnormalities, suggesting that PTHrP has a physiological function.

Interactions[edit]

Parathyroid hormone-related protein has been shown to interact with KPNB1[5][6] and Arrestin beta 1.[7]

References[edit]

  1. ^ Hens JR, Dann P, Zhang JP, Harris S, Robinson GW, Wysolmerski J (March 2007). "BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction". Development (Cambridge, England) 134 (6): 1221–30. doi:10.1242/dev.000182. PMID 17301089. 
  2. ^ Hens JR, Wysolmerski JJ (2005). "Key stages of mammary gland development: Molecular mechanisms involved in the formation of the embryonic mammary gland". Breast Cancer Research : BCR 7 (5): 220–4. doi:10.1186/bcr1306. PMC 1242158. PMID 16168142. 
  3. ^ Broadus AE, Mangin M, Ikeda K, Insogna KL, Weir EC, Burtis WJ, Stewart AF (September 1988). "Humoral hypercalcemia of cancer. Identification of a novel parathyroid hormone-like peptide". The New England Journal of Medicine 319 (9): 556–63. doi:10.1056/NEJM198809013190906. PMID 3043221. 
  4. ^ "Entrez Gene: PTHLH parathyroid hormone-like hormone". 
  5. ^ Cingolani, Gino; Bednenko Janna; Gillespie Matthew T; Gerace Larry (Dec 2002). "Molecular basis for the recognition of a nonclassical nuclear localization signal by importin beta". Mol. Cell (United States) 10 (6): 1345–53. doi:10.1016/S1097-2765(02)00727-X. ISSN 1097-2765. PMID 12504010. 
  6. ^ Lam, M H; Hu W; Xiao C Y; Gillespie M T; Jans D A (Mar 2001). "Molecular dissection of the importin beta1-recognized nuclear targeting signal of parathyroid hormone-related protein". Biochem. Biophys. Res. Commun. (United States) 282 (2): 629–34. doi:10.1006/bbrc.2001.4607. ISSN 0006-291X. PMID 11401507. 
  7. ^ Conlan, Lindus A; Martin T John; Gillespie Matthew T (Sep 2002). "The COOH-terminus of parathyroid hormone-related protein (PTHrP) interacts with beta-arrestin 1B". FEBS Lett. (Netherlands) 527 (1–3): 71–5. doi:10.1016/S0014-5793(02)03164-2. ISSN 0014-5793. PMID 12220636. 


Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.