Linked Life Data

20826165

Source:http://linkedlifedata.com/resource/pubmed/id/20826165

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-10-4
pubmed:abstractText
The Tec family kinases are tyrosine kinases that function primarily in hematopoietic cells. The catalytic activity of the Tec kinases is positively influenced by the regulatory domains outside of the kinase domain. The current lack of a full-length Tec kinase structure leaves a void in our understanding of how these positive regulatory signals are transmitted to the kinase domain. Recently, a conserved structure within kinases, the 'regulatory spine', which assembles and disassembles as a kinase switches between its active and inactive states, has been identified. Here, we define the residues that comprise the regulatory spine within Tec kinases. Compared to previously characterized systems, the Tec kinases contain an extended regulatory spine that includes a conserved methionine within the C-helix and a conserved tryptophan within the Src homology 2-kinase linker of Tec kinases. This extended regulatory spine forms a conduit for transmitting the presence of the regulatory domains of Tec kinases to the catalytic domain. We further show that mutation of the gatekeeper residue at the edge of the regulatory spine stabilizes the regulatory spine, resulting in a constitutively active kinase domain. Importantly, the regulatory spine is preassembled in this gatekeeper mutant, rendering phosphorylation on the activation loop unnecessary for its activity. Moreover, we show that the disruption of the conserved electrostatic interaction between Bruton's tyrosine kinase R544 on the activation loop and Bruton's tyrosine kinase E445 on the C-helix also aids in the assembly of the regulatory spine. Thus, the extended regulatory spine is a key structure that is critical for maintaining the activity of Tec kinases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
403
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
231-42
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Identification of an allosteric signaling network within Tec family kinases.
pubmed:affiliation
Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural