Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1991-11-18
pubmed:abstractText
The differential effect of cAMP on the regulation of early biochemical and cellular functions mediated through two different receptors on murine B cells are reported here. Surface IgM, the Ag receptor, and Lyb2, a 45-kDa differentiation Ag are concomitantly expressed on mature murine B lymphocytes. Triggering of B cells through these molecules, independently, resulted in inositol 1,4,5-triphosphate (IP3) generation, increase in intracellular Ca2+ levels, and cell enlargement associated with progression of cells from G0 to G1 ultimately resulting in DNA synthesis. Pretreatment of resting B cells with cholera toxin as well as other agents that raise the intracellular cAMP [(cAMP)i] such as forskolin, N6,2'-O-dibutyryl cyclic AMP, and 3-isobutyl-1 methyl xanthine inhibited the Ag receptor but not Lyb2-mediated DNA synthesis. The elevation of (cAMP)i inhibited the surface IgM but not Lyb2-mediated IP3 generation, Ca2+ response, and progression from G0 to G1 phase of the cell cycle. Failure of forskolin or N6,2'-O-dibutyryl cyclic AMP to inhibit Lyb2-mediated responses did not appear to be due to induction of cAMP-specific phosphodiesterase activity. Concentrations of H8 [N-(2-(methylamino)-ethyl)-5-isoquinoline sulfonamide, diHCl] inhibitory to cAMP dependent PKA prevented the inhibitory effect of forskolin on surface IgM-mediated Ca2+ response, suggesting that cAMP exerted its effects through PKA. These findings suggest that distinct PLC-coupled receptors, such as sIgM and Lyb2 molecules in B cells, may use either alternative mechanisms for phosphatidylinositol 4,5-bisphosphate hydrolysis or may use different intermediary transducer molecules that differ in their sensitivity to increased (cAMP)i levels. Thus "cross-talk" among cAMP and phosphatidylinositol signaling pathways was demonstrated for IgM but not Lyb2-mediated B cell activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
147
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2483-92
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:1717562-1-Methyl-3-isobutylxanthine, pubmed-meshheading:1717562-Animals, pubmed-meshheading:1717562-Antigens, Ly, pubmed-meshheading:1717562-B-Lymphocytes, pubmed-meshheading:1717562-Calcium, pubmed-meshheading:1717562-Cholera Toxin, pubmed-meshheading:1717562-Cyclic AMP, pubmed-meshheading:1717562-Female, pubmed-meshheading:1717562-Forskolin, pubmed-meshheading:1717562-Hydrolysis, pubmed-meshheading:1717562-Lymphocyte Activation, pubmed-meshheading:1717562-Mice, pubmed-meshheading:1717562-Mice, Inbred Strains, pubmed-meshheading:1717562-Phosphatidylinositols, pubmed-meshheading:1717562-Protein Kinases, pubmed-meshheading:1717562-Receptors, Antigen, pubmed-meshheading:1717562-Receptors, Antigen, B-Cell, pubmed-meshheading:1717562-Receptors, Transferrin, pubmed-meshheading:1717562-Signal Transduction
pubmed:year
1991
pubmed:articleTitle
Differential regulation of surface Ig- and Lyb2-mediated B cell activation by cyclic AMP. I. Evidence for alternative regulation of signaling through two different receptors linked to phosphatidylinositol hydrolysis in murine B cells.
pubmed:affiliation
Department of Microbiology and Immunology, University of Kentucky, Lexington 40536.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.