Linked Life Data

11487585

Source:http://linkedlifedata.com/resource/pubmed/id/11487585

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
48
pubmed:dateCreated
2001-11-23
pubmed:abstractText
B cell linker protein (BLNK) is a SLP-76-related adaptor protein essential for signal transduction from the BCR. To identify components of BLNK-associated signaling pathways, we performed a phosphorylation-dependent yeast two-hybrid analysis using BLNK probes. Here we report that the serine/threonine kinase hematopoietic progenitor kinase 1 (HPK1), which is activated upon antigen-receptor stimulation and which has been implicated in the regulation of MAP kinase pathways, interacts physically and functionally with BLNK in B cells and with SLP-76 in T cells. This interaction requires Tyr(379) of HPK1 and the Src homology 2 (SH2) domain of BLNK/SLP-76. Via homology modeling, we defined a consensus binding site within ligands for SLP family SH2 domains. We further demonstrate that the SH2 domain of SLP-76 participates in the regulation of AP-1 and NFAT activation in response to T cell receptor (TCR) stimulation and that HPK1 inhibits AP-1 activation in a manner partially dependent on its interaction with SLP-76. Our data are consistent with a model in which full activation of HPK1 requires its own phosphorylation on tyrosine and subsequent interaction with adaptors of the SLP family, providing a mechanistic basis for the integration of this kinase into antigen receptor signaling cascades.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
45207-16
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11487585-Adaptor Proteins, Signal Transducing, pubmed-meshheading:11487585-Animals, pubmed-meshheading:11487585-Binding Sites, pubmed-meshheading:11487585-Carrier Proteins, pubmed-meshheading:11487585-Cell Line, pubmed-meshheading:11487585-DNA, Complementary, pubmed-meshheading:11487585-Databases as Topic, pubmed-meshheading:11487585-Enzyme Activation, pubmed-meshheading:11487585-Humans, pubmed-meshheading:11487585-Immunoblotting, pubmed-meshheading:11487585-Jurkat Cells, pubmed-meshheading:11487585-Lymphocytes, pubmed-meshheading:11487585-Mice, pubmed-meshheading:11487585-Mice, Inbred C57BL, pubmed-meshheading:11487585-Models, Biological, pubmed-meshheading:11487585-Models, Molecular, pubmed-meshheading:11487585-Mutagenesis, Site-Directed, pubmed-meshheading:11487585-Mutation, pubmed-meshheading:11487585-Phosphoproteins, pubmed-meshheading:11487585-Precipitin Tests, pubmed-meshheading:11487585-Protein Binding, pubmed-meshheading:11487585-Protein Structure, Tertiary, pubmed-meshheading:11487585-Protein-Serine-Threonine Kinases, pubmed-meshheading:11487585-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11487585-Sequence Homology, Amino Acid, pubmed-meshheading:11487585-Signal Transduction, pubmed-meshheading:11487585-T-Lymphocytes, pubmed-meshheading:11487585-Transcription Factor AP-1, pubmed-meshheading:11487585-Two-Hybrid System Techniques, pubmed-meshheading:11487585-Up-Regulation, pubmed-meshheading:11487585-src Homology Domains
pubmed:year
2001
pubmed:articleTitle
Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes.
pubmed:affiliation
Department of Immunology and Rheumatology and Department of Molecular Systems, Merck Research Laboratories, Rahway, New Jersey 07065, USA. Karsten_Sauer@Merck.com
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.