Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1998-11-23
pubmed:abstractText
The T-cell antigen receptor (TCR) triggers a signaling cascade initiated by the tyrosine kinase Lck and requiring the proto-oncogene p95(vav). Vav is activated by Lck and can function as a guanine nucleotide exchange factor for the Rho-family GTPases, Rac1 and Cdc42. To investigate the involvement of these GTPases in TCR signaling, we focused on their well characterized effector, Pak1. This serine/threonine kinase is activated by GTP-bound Rac1 or Cdc42. However, its role in mediating downstream signaling events is controversial. We observed rapid, TCR-dependent activation of Pak1 and TCR-inducible association of Pak1 with Nck, which was tyrosine phosphorylated following stimulation. Pak1 activation occurred independently of Ras activation or calcium flux, but was dependent on the Lck tyrosine kinase, and was downstream of Vav and Cdc42. Dominant negative Pak1 or Nck specifically inhibited TCR-mediated activation of the nuclear factor of activated T cells (NFAT) transcription factor. TCR-mediated activation of Erk2 was also inhibited by dominant negative Pak. However, Pak1 activation was neither necessary nor sufficient for TCR-dependent c-Jun N-terminal kinase (JNK) activation. Therefore, Pak1 acts downstream of Vav and is required for activation of Erk2 and NFAT by a JNK-independent pathway. This is the first demonstration of a requirement for Pak to mediate the regulation of gene expression by an extracellular ligand.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-1311423, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-1377362, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-1505025, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-1531699, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-1698283, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-17708935, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-2201921, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-2234059, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-3263650, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-3920341, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-6208306, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7493928, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7499279, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7592586, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7592896, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7600581, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7600582, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7618083, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7623828, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7700358, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7700359, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7700360, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7744004, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-7761442, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8107774, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8205621, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8228805, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8376929, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8627172, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8670897, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8702668, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8791419, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8798379, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8805275, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8808675, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8824201, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8898204, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8939567, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-8990121, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9024622, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9032240, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9032259, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9032261, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9069257, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9109498, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9150145, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9351825, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9395435, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9438836, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9601639, http://linkedlifedata.com/resource/pubmed/commentcorrection/9755165-9601640
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent..., http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein..., http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Specific Protein..., http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Nck protein, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/PAK1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/p21-Activated Kinases
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0261-4189
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5647-57
pubmed:dateRevised
2009-11-19
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