scholarly journals Cyclic AMP Stimulates SF-1-Dependent CYP11A1 Expression through Homeodomain-Interacting Protein Kinase 3-Mediated Jun N-Terminal Kinase and c-Jun Phosphorylation

2007 ◽  
Vol 27 (6) ◽  
pp. 2027-2036 ◽  
Author(s):  
Hsin-Chieh Lan ◽  
Hua-Jung Li ◽  
Guang Lin ◽  
Pao-Yen Lai ◽  
Bon-chu Chung
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Functional Interaction ◽  
Interacting Protein ◽  
Surface Receptors ◽  
Camp Signaling Pathway ◽  
Camp Stimulation

ABSTRACT Steroids are synthesized in adrenal glands and gonads under the control of pituitary peptides. These peptides bind to cell surface receptors to activate the cyclic AMP (cAMP) signaling pathway leading to an increase of steroidogenic gene expression. Exactly how cAMP activates steroidogenic gene expression is not clear, except for the knowledge that transcription factor SF-1 plays a key role. Investigating the factors participating in SF-1 action, we found that c-Jun and homeodomain-interacting protein kinase 3 (HIPK3) were required for basal and cAMP-stimulated expression of one major steroidogenic gene, CYP11A1. HIPK3 enhanced SF-1 activity, and c-Jun was required for the functional interaction of HIPK3 with SF-1. Furthermore, after cAMP stimulation, both c-Jun and Jun N-terminal kinase (JNK) were phosphorylated through HIPK3. These phosphorylations were important for SF-1 activity and CYP11A1 expression. Thus, we have defined HIPK3-mediated JNK activity and c-Jun phosphorylation as important events that increase SF-1 activity for CYP11A1 transcription in response to cAMP. This finding has linked three common factors, HIPK3, JNK, and c-Jun, to the cAMP signaling pathway leading to increased steroidogenic gene expression.

scholarly journals Role of Actin Cytoskeletal Dynamics in Activation of the Cyclic AMP Pathway and HWP1 Gene Expression in Candida albicans

2007 ◽  
Vol 6 (10) ◽  
pp. 1824-1840 ◽  
Author(s):  
Michael J. Wolyniak ◽  
Paula Sundstrom
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Cyclic Amp ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Specific Gene ◽  
Camp Signaling Pathway ◽  
Hypha Formation ◽  
Cytoskeletal Dynamics ◽  
Opportunistic Fungal Pathogen

ABSTRACT Changes in gene expression during reversible bud-hypha transitions of the opportunistic fungal pathogen Candida albicans permit adaptation to environmental conditions that are critical for proliferation in host tissues. Our previous work has shown that the hypha-specific adhesin gene HWP1 is up-regulated by the cyclic AMP (cAMP) signaling pathway. However, little is known about the potential influences of determinants of cell morphology on HWP1 gene expression. We found that blocking hypha formation with cytochalasin A, which destabilizes actin filaments, and with latrunculin A, which sequesters actin monomers, led to a loss of HWP1 gene expression. In contrast, high levels of HWP1 gene expression were observed when the F-actin stabilizer jasplakinolide was used to block hypha formation, suggesting that HWP1 expression could be regulated by actin structures. Mutants defective in formin-mediated nucleation of F-actin were reduced in HWP1 gene expression, providing genetic support for the importance of actin structures. Kinetic experiments with wild-type and actin-deficient cells revealed two distinct phases of HWP1 gene expression, with a slow, actin-independent phase preceding a fast, actin-dependent phase. Low levels of HWP1 gene expression that appeared to be independent of stabilized actin and cAMP signaling were detected using indirect immunofluorescence. A connection between actin structures and the cAMP signaling pathway was shown using hyper- and hypomorphic cAMP mutants, providing a possible mechanism for up-regulation of HWP1 gene expression by stabilized actin. The results reveal a new role for F-actin as a regulatory agent of hypha-specific gene expression at the bud-hypha transition.

scholarly journals Cholera toxin induces expression of the immediate-early response gene JE via a cyclic AMP-independent signaling pathway.

1991 ◽  
Vol 11 (1) ◽  
pp. 102-107 ◽  
Author(s):  
S A Qureshi ◽  
K Alexandropoulos ◽  
C K Joseph ◽  
R Spangler ◽  
D A Foster
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Cholera Toxin ◽  
Signaling Pathway ◽  
Acid Metabolism ◽  
Early Response ◽  
Arachidonic Acid Metabolism ◽  
Immediate Early

Cholera toxin (CT) activates expression of two immediate-early response genes (JE and TIS10) in quiescent BALB/c 3T3 cells. Increases in cyclic AMP (cAMP) levels in response to CT are likely responsible for the induction of TIS10 gene expression, since treatment with 8-Br-cAMP and increasing the intracellular levels of cAMP by treatment with forskolin induce TIS10 gene expression. In contrast, neither forskolin nor 8-Br-cAMP induces JE gene expression. 3-Isobutyl-1-methylxanthine, which stabilizes intracellular cAMP, potentiates CT-induced TIS10 gene expression but has no effect on CT-induced JE gene expression. Thus, induction of JE by CT is independent of the cAMP produced in response to CT. Induction of JE by CT does not require protein kinase C (PKC), since depleting cells of PKC activity has no effect on the induction of JE by CT. CT-induced expression of JE can be distinguished from CT-induced TIS10 gene expression by using protein kinase inhibitors and inhibitors of arachidonic acid metabolism, further suggesting distinct signaling pathways for CT-induced JE and TIS10 gene expression. Thus, induction of JE gene expression by CT results from the activation of an intracellular signaling pathway that is independent of cAMP production. This pathway is independent of PKC activity and uniquely sensitive to inhibitors of protein kinases and arachidonic acid metabolism.

scholarly journals The cAMP Signaling Pathway and Direct Protein Kinase A Phosphorylation Regulate Polycystin-2 (TRPP2) Channel Function

2015 ◽  
Vol 290 (39) ◽  
pp. 23888-23896 ◽  
Author(s):  
María del Rocío Cantero ◽  
Irina F. Velázquez ◽  
Andrew J. Streets ◽  
Albert C. M. Ong ◽  
Horacio F. Cantiello
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Channel Function ◽  
Camp Signaling Pathway ◽  
Kinase A

scholarly journals Genome-Wide Transcriptional Profiling of the Cyclic AMP-Dependent Signaling Pathway during Morphogenic Transitions of Candida albicans

2007 ◽  
Vol 6 (12) ◽  
pp. 2376-2390 ◽  
Author(s):  
Yong-Sun Bahn ◽  
Matthew Molenda ◽  
Janet F. Staab ◽  
Courtney A. Lyman ◽  
Laura J. Gordon ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cyclic Amp ◽  
Signaling Pathway ◽  
Virulence Factors ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Camp Signaling ◽  
Phenotypic Traits ◽  
Null Mutant ◽  
Camp Signaling Pathway

ABSTRACT Candida albicans is an opportunistic human fungal pathogen that causes systemic candidiasis as well as superficial mucosal candidiasis. In response to the host environment, C. albicans transitions between yeast and hyphal forms. In particular, hyphal growth is important in facilitating adhesion and invasion of host tissues, concomitant with the expression of various hypha-specific virulence factors. In previous work, we showed that the cyclic AMP (cAMP) signaling pathway plays a crucial role in morphogenic transitions and virulence of C. albicans by studying genes encoding adenylate cyclase-associated protein (CAP1) and high-affinity phosphodiesterase (PDE2) (Y. S. Bahn, J. Staab, and P. Sundstrom, Mol. Microbiol. 50:391-409, 2003; and Y. S. Bahn and P. Sundstrom, J. Bacteriol. 183:3211-3223, 2001). However, little is known about the downstream targets of the cAMP signaling pathway that are responsible for morphological transitions and the expression of virulence factors. Here, microarrays were probed with RNA from strains with hypoactive (cap1/cap1 null mutant), hyperactive (pde2/pde2 null mutant), and wild-type cAMP signaling pathways to provide insight into the molecular mechanisms of virulence that are regulated by cAMP and that are related to the morphogenesis of C. albicans. Genes controlling metabolic specialization, cell wall structure, ergosterol/lipid biosynthesis, and stress responses were modulated by cAMP during hypha formation. Phenotypic traits predicted to be regulated by cAMP from the profiling results correlated with the relative strengths of the mutants when tested for resistance to azoles and subjected to heat shock stress and oxidative/nitrosative stress. The results from this study provide important insights into the role of the cAMP signaling pathway not only in morphogenic transitions of C. albicans but also for adaptation to stress and for survival during host infections.

scholarly journals Mechanistic Differences in the Activation of Estrogen Receptor-α (ERα)- and ERβ-dependent Gene Expression by cAMP Signaling Pathway(s)

2003 ◽  
Vol 278 (15) ◽  
pp. 12834-12845 ◽  
Author(s):  
Kevin M. Coleman ◽  
Martin Dutertre ◽  
Abeer El-Gharbawy ◽  
Brian G. Rowan ◽  
Nancy L. Weigel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Signaling Pathway ◽  
Estrogen Receptor Α ◽  
Camp Signaling ◽  
Camp Signaling Pathway

Lasp-1 is a regulated phosphoprotein within the cAMP signaling pathway in the gastric parietal cell

1998 ◽  
Vol 275 (1) ◽  
pp. C56-C67 ◽  
Author(s):  
C. S. Chew ◽  
J. A. Parente ◽  
C.-J. Zhou ◽  
E. Baranco ◽  
X. Chen
Keyword(s):  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Signaling Pathway ◽  
Parietal Cell ◽  
Cell Types ◽  
Parietal Cells ◽  
Camp Signaling ◽  
Gastric Parietal Cell ◽  
Putative Protein ◽  
Camp Signaling Pathway

Activation of the cAMP signaling pathway is correlated with increased secretory-related events in a wide variety of cell types including the gastric parietal cell. Within this pathway, as well as in other intracellular signaling pathways, protein phosphorylation serves as a major downstream regulatory mechanism. However, although agonist and cAMP-dependent activation of cAMP-dependent protein kinase (PKA) has been demonstrated, little is currently known about the downstream in vivo phosphoprotein substrates of this enzyme. Here we report the isolation, microsequencing, and cloning of a LIM and SH3 domain-containing, cAMP-responsive, 40-kDa phosphoprotein (pp40) from rabbit gastric parietal cells. The deduced amino acid sequence for pp40 is 93.5%, homologous with the putative protein product of the human gene lasp-1, which was recently identified based on its overexpression in some breast carcinomas. In addition to LIM and SH3 domains, the rabbit homolog contains two highly conserved PKA consensus sequences as well as two conserved SH2 binding motifs and several other putative protein kinase phosphorylation sites, including two for tyrosine kinase(s). Combined Northern and Western blot analyses indicate that pp40/lasp-1 is widely expressed (through a single 3.3-kb message) not only in epithelial tissues but also in muscle and brain. Furthermore, stimulation of isolated parietal cells, distal colonic crypts, and pancreatic cells with the adenylyl cyclase activator forskolin leads to the appearance of a higher molecular weight form of pp40/lasp-1, a finding which is consistent with an increase in protein phosphorylation. Thus pp40/lasp-1 appears to be regulated within the cAMP signaling pathway in a wide range of epithelial cell types. Because the cAMP-dependent increase in pp40 phosphorylation is correlated with secretory responses in the parietal cell and because pp40 appears to be widely distributed among various secretory tissues, this newly defined signaling protein may play an important role in modulating ionic transport or other secretory-related activities in many different cell types.

Cholera toxin induces expression of the immediate-early response gene JE via a cyclic AMP-independent signaling pathway

1991 ◽  
Vol 11 (1) ◽  
pp. 102-107
Author(s):  
S A Qureshi ◽  
K Alexandropoulos ◽  
C K Joseph ◽  
R Spangler ◽  
D A Foster
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Cholera Toxin ◽  
Signaling Pathway ◽  
Acid Metabolism ◽  
Early Response ◽  
Arachidonic Acid Metabolism ◽  
Immediate Early

Cholera toxin (CT) activates expression of two immediate-early response genes (JE and TIS10) in quiescent BALB/c 3T3 cells. Increases in cyclic AMP (cAMP) levels in response to CT are likely responsible for the induction of TIS10 gene expression, since treatment with 8-Br-cAMP and increasing the intracellular levels of cAMP by treatment with forskolin induce TIS10 gene expression. In contrast, neither forskolin nor 8-Br-cAMP induces JE gene expression. 3-Isobutyl-1-methylxanthine, which stabilizes intracellular cAMP, potentiates CT-induced TIS10 gene expression but has no effect on CT-induced JE gene expression. Thus, induction of JE by CT is independent of the cAMP produced in response to CT. Induction of JE by CT does not require protein kinase C (PKC), since depleting cells of PKC activity has no effect on the induction of JE by CT. CT-induced expression of JE can be distinguished from CT-induced TIS10 gene expression by using protein kinase inhibitors and inhibitors of arachidonic acid metabolism, further suggesting distinct signaling pathways for CT-induced JE and TIS10 gene expression. Thus, induction of JE gene expression by CT results from the activation of an intracellular signaling pathway that is independent of cAMP production. This pathway is independent of PKC activity and uniquely sensitive to inhibitors of protein kinases and arachidonic acid metabolism.

scholarly journals cAMP signaling pathway controls glycogen metabolism in Neurospora crassa by regulating the glycogen synthase gene expression and phosphorylation

2010 ◽  
Vol 47 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Fernanda Zanolli Freitas ◽  
Renato Magalhães de Paula ◽  
Luiz Carlos Bertucci Barbosa ◽  
Hector Francisco Terenzi ◽  
Maria Célia Bertolini
Keyword(s):  
Gene Expression ◽  
Neurospora Crassa ◽  
Signaling Pathway ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Camp Signaling ◽  
Camp Signaling Pathway

scholarly journals Stimulation of GCMa Transcriptional Activity by Cyclic AMP/Protein Kinase A Signaling Is Attributed to CBP-Mediated Acetylation of GCMa

2005 ◽  
Vol 25 (19) ◽  
pp. 8401-8414 ◽  
Author(s):  
Ching-Wen Chang ◽  
Hsiao-Ching Chuang ◽  
Chenchou Yu ◽  
Tso-Pang Yao ◽  
Hungwen Chen
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Transcriptional Activation ◽  
Transcriptional Activity ◽  
Camp Signaling ◽  
Transactivation Domain ◽  
Dependent Protein ◽  
Kinase A

ABSTRACT Human GCMa is a zinc-containing transcription factor primarily expressed in placenta. GCMa regulates expression of syncytin gene, which encodes for a placenta-specific membrane protein that mediates trophoblastic fusion and the formation of syncytiotrophoblast layer required for efficient fetal-maternal exchange of nutrients and oxygen. The adenylate cyclase activator, forskolin, stimulates syncytin gene expression and cell fusion in cultured placental cells. Here we present evidence that cyclic AMP (cAMP) signaling pathway activates the syncytin gene expression by regulating GCMa activity. We found that forskolin and protein kinase A (PKA) enhances GCMa-mediated transcriptional activation. Furthermore, PKA treatment stimulates the association of GCMa with CBP and increases GCMa acetylation. CBP primarily acetylates GCMa at lysine367, lysine406, and lysine409 in the transactivation domain (TAD). We found that acetylation of these residues is required to protect GCMa from ubiquitination and increases the TAD stability with a concomitant increase in transcriptional activity, supporting the importance of acetylation in PKA-dependent GCMa activation. Our results reveal a novel regulation of GCMa activity by cAMP-dependent protein acetylation and provide a molecular mechanism by which cAMP signaling regulates trophoblastic fusion.

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