Linked Life Data

20160094

Source:http://linkedlifedata.com/resource/pubmed/id/20160094

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-3-3
pubmed:abstractText
The p38alpha/beta mitogen-activated protein kinase (MAPK) pathway promotes muscle-specific gene expression and myoblast differentiation but how pathway activity is initiated during these processes is poorly understood. During myoblast differentiation, the intracellular region of the promyogenic cell surface protein Cdo (also known as Cdon) binds to Bnip-2 and JLP, scaffold proteins for Cdc42 and p38alpha/beta MAPK, respectively. The Bnip-2/Cdc42 and JLP/p38alpha/beta complexes associate in a Cdo-dependent manner, resulting in Bnip-2/Cdc42-dependent p38alpha/beta activation and stimulation of cell differentiation. Although the Cdo ectodomain binds to several different proteins, it is unclear how Cdo-dependent p38alpha/beta activation is initiated. In myoblasts, Cdo interacts with the cell-cell adhesion molecule N-cadherin. Cdo also binds directly to the secreted morphogen Sonic hedgehog (Shh) to promote Shh pathway signaling. We report here that N-cadherin ligation activates p38alpha/beta in myoblasts in a Cdo-, Bnip-2-, and JLP-dependent manner. Furthermore, these proteins and activated Cdc42 cluster at sites of N-cadherin ligation. In contrast, neither JLP nor Bnip-2 is associated with Cdo bound to Shh, and Shh does not activate p38alpha/beta in myoblasts. Taken together, these results link cadherin-based cell-cell adhesion to a defined signaling pathway (Cdo --> p38alpha/beta) that directly regulates a cell-type-specific differentiation program. Furthermore, they are consistent with a model whereby Cdo serves as a multifunctional coreceptor with mechanistically distinct roles in multiple signaling pathways.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
107
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4212-7
pubmed:dateRevised
2010-9-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
N-cadherin ligation, but not Sonic hedgehog binding, initiates Cdo-dependent p38alpha/beta MAPK signaling in skeletal myoblasts.
pubmed:affiliation
Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural