Linked Life Data

19357398

Source:http://linkedlifedata.com/resource/pubmed/id/19357398

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2009-5-29
pubmed:abstractText
Matriptase-2 is a transmembrane serine protease that negatively regulates hepcidin expression by cleaving membrane-bound hemojuvelin. Matriptase-2 has a complex ectodomain, including a C-terminal serine protease domain and its activation requires an autocatalytic cleavage. Matriptase-2 mutations have been reported in several patients with iron-refractory iron deficiency anemia. Here we describe a patient with 2 missense mutations in the second class A low-density lipoprotein receptor (LDLRA) domain. Functional studies of these 2 mutations and of a previously reported mutation in the second C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1 (CUB) domain were performed. Transfection of mutant cDNAs showed that membrane targeting of the 2 LDLRA mutants was impaired, with Golgi retention of the variants. The activating cleavage was absent for the LDLRA mutants and reduced for the CUB mutant. All 3 mutated proteins were still able to physically interact with hemojuvelin but only partially repressed hepcidin expression compared with wild-type matriptase-2. Our results underline the importance of LDLRA and CUB domains of matriptase-2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5605-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia.
pubmed:affiliation
Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't