Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
27
pubmed:dateCreated
2000-8-16
pubmed:abstractText
Stimulation of beta-adrenergic receptor normally results in signaling by the heterotrimeric G protein G(s), leading to the activation of adenylyl cyclase, production of cAMP, and activation of cAMP-dependent protein kinase (PKA). Here we report that cell death of thymocytes can be induced after stimulation of beta-adrenergic receptor, or by addition of exogenous cAMP. Apoptotic cell death in both cases was observed with the appearance of terminal deoxynucleotidyl transferase-mediated UTP end labeling reactivity and the activation of caspase-3 in S49 T cells. Using thymocytes deficient in either Galpha(s) or PKA, we find that engagement of beta-adrenergic receptors initiated a Galpha(s)-dependent, PKA-independent pathway leading to apoptosis. This alternative pathway involves Src family tyrosine kinase Lck. Furthermore, we show that Lck protein kinase activity can be directly stimulated by purified Galpha(s). Our data reveal a new signaling pathway for Galpha(s), distinct from the classical PKA pathway, that accounts for the apoptotic action of beta-adrenergic receptors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20726-33
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10767282-Animals, pubmed-meshheading:10767282-Apoptosis, pubmed-meshheading:10767282-Cell Survival, pubmed-meshheading:10767282-Cyclic AMP, pubmed-meshheading:10767282-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:10767282-Flow Cytometry, pubmed-meshheading:10767282-GTP-Binding Proteins, pubmed-meshheading:10767282-In Situ Nick-End Labeling, pubmed-meshheading:10767282-Isoproterenol, pubmed-meshheading:10767282-Lymphocyte Specific Protein Tyrosine Kinase p56(lck), pubmed-meshheading:10767282-Lymphoma, pubmed-meshheading:10767282-Mice, pubmed-meshheading:10767282-Mutation, pubmed-meshheading:10767282-Receptors, Adrenergic, beta, pubmed-meshheading:10767282-Signal Transduction, pubmed-meshheading:10767282-T-Lymphocytes, pubmed-meshheading:10767282-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Apoptotic signaling through the beta -adrenergic receptor. A new Gs effector pathway.
pubmed:affiliation
Graduate Program of Cell Biology and Genetics, Graduate Program of Physiology, Biophysics and Molecular Medicine, and the Department of Physiology, Cornell University Medical College, New York, New York 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't