Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1998-7-1
pubmed:databankReference
pubmed:abstractText
We have previously identified and partially cloned Band 17, a gene expressed in growth plate chondrocytes transiting from proliferation to hypertrophy. We now rename this gene HiPER1, Histidine Phosphatase of the Endoplasmic Reticulum-1, based on the results reported here. HiPER1 encodes two proteins of 318 (HiPER1(318)) and 449 (HiPER1(449)) amino acids, which are 20-21% identical to a group of yeast acid phosphatases that are in the histidine phosphatase family. HiPER1(449) is significantly more abundant than HiPER1(318), correlating with the abundance of the alternatively spliced messages encoding HiPER449 and HiPER318. Anti-HiPER1 antibodies detect two proteins of 53 and 55 kDa in growth plate chondrocytes that are absent in articular chondrocytes. We confirm that the 53 and 55 kDa proteins are HiPER1(449) by heterologous expression of the HiPER1(449) coding sequence in chick embryo fibroblasts. The 53 and 55 kDa proteins are glycosylated forms of HiPER1(449), as N-glycosidase F digestion reduces these proteins to 48 kDa, the predicted size of HiPER1(449) without the N-terminal signal sequence. Immunocytochemistry demonstrates that HiPER1(449) is found in chondrocytes maturing from proliferation to hypertrophy, but is not detectable in resting zone, deep hypertrophic zone or articular chondrocytes, a distribution that is consistent with the message distribution. HiPER1(449) was predicted to localize to the lumen of endoplasmic reticulum by an N-terminal signal sequence and by the C-terminal sequence Ala-Asp-Glu-Leu, which closely matches the consensus signal for ER retention, Lys-Asp-Glu-Leu. We confirm this prediction by demonstrating colocalization of HiPER1(449) with the ER protein HSP47 using dual-label immunofluorescence. PTHrP, a peptide that prevents hypertrophy in chondrocytes, suppressed HiPER1 and HiPER1(449) expression in vitro, an observation that further supports a role for HiPER1 in chondrocyte maturation. The yeast phosphatase homology, localization to the endoplasmic reticulum and pattern of expression suggest that HiPER1 represents a previously unrecognized intracellular pathway, involved in differentiation of chondrocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:volume
111 ( Pt 6)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
803-13
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9472008-Amino Acid Sequence, pubmed-meshheading:9472008-Animals, pubmed-meshheading:9472008-Base Sequence, pubmed-meshheading:9472008-Cell Differentiation, pubmed-meshheading:9472008-Cell Division, pubmed-meshheading:9472008-Chick Embryo, pubmed-meshheading:9472008-Chondrocytes, pubmed-meshheading:9472008-Endoplasmic Reticulum, pubmed-meshheading:9472008-Glycosylation, pubmed-meshheading:9472008-Growth Plate, pubmed-meshheading:9472008-Histidine, pubmed-meshheading:9472008-Isoenzymes, pubmed-meshheading:9472008-Molecular Sequence Data, pubmed-meshheading:9472008-Molecular Weight, pubmed-meshheading:9472008-Parathyroid Hormone, pubmed-meshheading:9472008-Parathyroid Hormone-Related Protein, pubmed-meshheading:9472008-Phosphoric Monoester Hydrolases, pubmed-meshheading:9472008-Proteins, pubmed-meshheading:9472008-RNA, Messenger, pubmed-meshheading:9472008-Sequence Homology, Amino Acid
pubmed:year
1998
pubmed:articleTitle
HiPER1, a phosphatase of the endoplasmic reticulum with a role in chondrocyte maturation.
pubmed:affiliation
Department of Orthopaedics, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.