Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Engagement of membrane IgM on a number of human and murine B-cell lines induced activation of a Mn(2+)-preferring serine/threonine kinase that phosphorylated microtubule-associated protein-2 (MAP-2) in vitro. B-cell MAP-2 kinase (MAP-2K) activity could be fractionated into two peaks by sequential DEAE and hydrophobic chromatography. Although peak I included two tyrosine phosphoproteins of molecular mass 36 and 38 kDa, peak II showed a single 42-kDa tyrosine phosphoprotein (pp42). Since all kinase activity could be removed from peak II material over an antiphosphotyrosine immune affinity column, it suggests that pp42 is identical with lymphoid MAP-2K. Although peak I activity showed a similarity to peak II with regard to its preference for Mn2+, sensitivity to phosphatase exposure, and resistance to a range of common serine kinase inhibitors, it is not clear whether these activities are related. MAP-2 kinase activity could also be induced by treatment with the phorbol ester, phorbol myristate 13-acetate, suggesting that protein kinase C may also be involved with MAP-2K regulation. Although MAP-2K activity reached a peak response within minutes of receptor ligation, there were differences in the rates of dephosphorylation of pp42 and decline of MAP-2K activity in different B-cell lines. The tyrosine phosphatase inhibitor, vanadate, transformed a rapidly reversible MAP-2K response in BAL 17.2 cells into a sustained state of activation that resembled the kinetics of activation in WEHI-231 cells. The latter finding implies involvement of a tyrosine phosphatase, which opposes the effect of an inducing tyrosine kinase.
 ...
PMID:Stimulation of B-cells via the membrane immunoglobulin receptor or with phorbol myristate 13-acetate induces tyrosine phosphorylation and activation of a 42-kDa microtubule-associated protein-2 kinase. 165 69

Binding of cyclic AMP (cAMP) to cell surface receptors induces activation and adaptation of adenylate cyclase while 2,3-dimercapto-1-propanol (BAL) acts only on the activation pathway. Here we show that an inhibitor of protein kinase (K252a) inhibits the cAMP-induced activation of the cyclase but not (rather enhances) the BAL-induced activation. These results suggest that protein kinase is involved in transduction of the activation signal and that phosphorylation might take place between the receptor and the action site of BAL. Since adaptation causes cessation of the activation, the enhancement of the BAL-induced cAMP accumulation by K252a might imply that K252a also blocks transduction of the adaptation signal.
 ...
PMID:Involvement of protein kinase(s) in the intracellular signal transduction pathways for activation and adaptation of adenylate cyclase in Dictyostelium discoideum. 215 15

We previously reported that cross-linking surface immunoglobulin (sIg) leads to induction of the transcription factor CREB in B lymphocytes through phosphorylation at Ser133, despite the lack of an increase in cAMP. Further, cAMP-raising agents fail to induce CREB Ser133 phosphorylation and CRE-dependent gene expression in these cells, which differs sharply from the situation in PC12 rat pheochromocytoma cells where CREB responds to elevation of cAMP through the activity of protein kinase A. In this study, we characterized the signal transduction pathways leading from sIg engagement to CREB activation. By using specific inhibitors for protein kinase C (PKC), Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), and protein kinase A (PKA), we found that anti-Ig-induced CREB Ser133 phosphorylation depends on PKC, but does not require activation of PKA or CaM kinase II. The differential responsiveness of CREB to forskolin in PC12 cells and BAL-17 B cells may relate to the more marked elevation of cAMP in the former as opposed to the latter; however, high concentrations of dbcAMP which should readily enter B cells and artificially increase cAMP levels still failed to induce CREB Ser133 phosphorylation, even in conjunction with a phosphodiesterase inhibitor. Taken together, the cAMP/PKA pathway does not appear to be as active a contributor to CREB phosphorylation in B lymphocytes as in PC12 cells, and does not appear to be involved in sIg-induced, PKC-dependent, CREB activation.
 ...
PMID:Signaling pathways for antigen receptor-mediated induction of transcription factor CREB in B lymphocytes. 862 May 54

Engagement of surface immunoglobulin on mature B cells leads to rescue from apoptosis and to proliferation. Levels of bcl-2 mRNA and protein increase with cross-linking of surface immunoglobulin. We have located the major positive regulatory region for control of bcl-2 expression in B cells in the 5'-flanking region. The positive region can be divided into an upstream and a downstream regulatory region. The downstream regulatory region contains a cyclic AMP-responsive element (CRE). We show by antibody supershift experiments and UV cross-linking followed by denaturing polyacrylamide gel electrophoresis that both CREB and ATF family members bind to this region in vitro. Mutations of the CRE site that result in loss of CREB binding also lead to loss of functional activity of the bcl-2 promoter in transient-transfection assays. The presence of an active CRE site in the bcl-2 promoter implies that the regulation of bcl-2 expression is linked to a signal transduction pathway in B cells. Treatment of the mature B-cell line BAL-17 with either anti-immunoglobulin M or phorbol 12-myristate 13-acetate leads to an increase in bcl-2 expression that is mediated by the CRE site. Treatment of the more immature B-cell line, Ramos, with phorbol esters rescues the cells from calcium-dependent apoptosis. bcl-2 expression is increased following phorbol ester treatment, and the increased expression is dependent on the CRE site. These stimuli result in phosphorylation of CREB at serine 133. The phosphorylation of CREB that results in activation is mediated by protein kinase C rather than by protein kinase A. Although the CRE site is necessary, optimal induction of bcl-2 expression requires participation of the upstream regulatory element, suggesting that phosphorylation of CREB alters its interaction with the upstream regulatory element. The CRE site in the bcl-2 promoter appears to play a major role in the induction of bcl-2 expression during the activation of mature B cells and during the rescue of immature B cells from apoptosis. It is possible that the CRE site is responsible for induction of bcl-2 expression in other cell types, particularly those in which protein kinase C is involved.
 ...
PMID:Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis. 881 67