Linked Life Data

18329366

Source:http://linkedlifedata.com/resource/pubmed/id/18329366

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-3-10
pubmed:abstractText
Certain autoimmune diseases result in abnormal bone homeostasis, but association of immunodeficiency with bone is poorly understood. Osteoclasts, which derive from bone marrow cells, are under the control of the immune system. Differentiation of osteoclasts is mainly regulated by signaling pathways activated by RANK and immune receptors linked to ITAM-harboring adaptors. However, it is unclear how the two signals merge to cooperate in osteoclast differentiation. Here we report that mice lacking the tyrosine kinases Btk and Tec show severe osteopetrosis caused by a defect in bone resorption. RANK and ITAM signaling results in formation of a Btk(Tec)/BLNK(SLP-76)-containing complex and PLCgamma-mediated activation of an essential calcium signal. Furthermore, Tec kinase inhibition reduces osteoclastic bone resorption in models of osteoporosis and inflammation-induced bone destruction. Thus, this study reveals the importance of the osteoclastogenic signaling complex composed of tyrosine kinases, which may provide the molecular basis for a new therapeutic strategy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1097-4172
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
132
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
794-806
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals.
pubmed:affiliation
Department of Cell Signaling, Graduate School, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't