| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Epac 1 ( cAMP GEFI ) and Epac 2 ( cAMP GEFII ) are closely related guanine nucleotide exchange factors ( GEFs ) for the small GTPase Rap 1 , which are directly regulated by cAMP . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| We also show that Rac activation results from activation of Rap 1 through the cAMP guanine nucleotide exchange factor ( GEF ) Epac 1 . ^^^ Indeed , Epac 1 regulates secretion of the non amyloidogenic soluble form of APP ( sAPPalpha ) through Rap 1 and Rac . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Among circulating hematopoietic cells , B CLL uniquely expresses functional EPAC 1 , but EPAC 1 mediated Rap 1 activation does not account for PDE 4 inhibitor induced apoptosis . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| We report here that the small GTPase Rap 1 regulates the adhesion of a number of cell lines to various extracellular matrix proteins including laminin 5 . cAMP also mediates cell adhesion and spreading on laminin 5 , a process that is independent of protein kinase A but rather dependent on Epac 1 , a cAMP dependent exchange factor for Rap . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Epac 1 is a guanine nucleotide exchange factor for Rap 1 that is activated by direct binding of cAMP . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| PKA independent activation of Rap 1 by cAMP is mediated by direct binding of cAMP to Rap 1 guanine nucleotide exchange factors ( Rap 1 GEFs ) Epac 1 ( exchange protein directly activated by cAMP 1 ) and Epac 2 ( Epac 1 and Epac 2 are also called cAMP GEFI and GEFII ) . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Antibodies directed against either the cAMP activated guanine nucleotide exchange factor Epac 1 , the monomeric G protein Rap 1 or the kinase Raf B , curtailed the stimulation of H , K ATPase by calcitonin , whereas antibodies against the related monomeric G protein Ras or kinase Raf 1 had no effect . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| However , cAMP also directly regulates Epac 1 and Epac 2 , guanine nucleotide exchange factors ( GEFs ) for the small GTPases Rap 1 and Rap 2 ( refs 2 , 3 ) . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Epac 1 is a guanine nucleotide exchange factor ( GEF ) for the small GTPase Rap 1 that is directly activated by cAMP . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Epac 1 and 2 ( exchange proteins directly activated by cyclic AMP ) are guanine nucleotide exchange factors for the GTPases Rap 1 and 2 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| In this study , we demonstrate the presence of Epac 1 in human peripheral blood monocytes and activation of Rap 1 in response to cAMP . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Epac is a Rap 1 guanine nucleotide exchange factor directly activated by cyclic AMP . ^^^ Epac binds cAMP in vitro and exhibits in vivo and in vitro GEF activity towards Rap 1 . cAMP strongly induces the GEF activity of Epac towards Rap 1 both in vivo and in vitro . ^^^ We conclude that Epac is a GEF for Rap 1 that is regulated directly by cAMP and that Epac is a new target protein for cAMP . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| MAP1A light chain 2 interacts with exchange protein activated by cyclic AMP 1 ( EPAC 1 ) to enhance Rap 1 GTPase activity and cell adhesion . ^^^ In the present study we used a simultaneous expression system and found that LC 2 enhances both basal and 8 ( 4 chloro phenylthio ) 2 ' O methyladenosine 3 ' : 5 ' cyclic monophosphate ( 8 CPT 2Me cAMP ) stimulated Rap 1 activation by EPAC 1 . ^^^ Nocodazole inhibited Rap 1 activity in cells transfected with EPAC 1 alone but had little effect on Rap 1 activity in cells transfected with both EPAC 1 and LC 2 . ^^^ We also found that disruption of the interaction of endogenous EPAC 1 and LC 2 with antibodies to the cAMP domain of EPAC 1 abolished Rap 1 activity in PC 12 cell lysates , demonstrating the importance of LC 2 for EPAC 1 activation in these cells . ^^^ LC 2 is therefore a biological enhancer of EPAC 1 activity toward Rap 1 and associated downstream signaling mechanisms . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| We have previously shown that Rap 1 as well as its guanine nucleotide exchange factor Epac 1 increases cell cell junction formation . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Immunoprecipitation of Epac 1 in forskolin stimulated cells co immunoprecipitated Rap 1 , p Akt ( Thr 308 ) , and p Akt ( Ser 473 ) . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| PDE4D3 also functions as an adaptor protein that recruits Epac 1 , an exchange factor for the small GTPase Rap 1 , to enable cAMP dependent attenuation of ERK 5 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Elevation of the intracellular cAMP concentration ( [ cAMP ] 1 ) regulates metabolism , cell proliferation , and differentiation and plays roles in memory formation and neoplastic growth . cAMP mediates its effects mainly through activation of protein kinase A ( PKA ) as well as Epac 1 and Epac 2 , exchange factors activating the small GTPases Rap 1 and Rap 2 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Overexpresssion of an isolated CAT domain in COS 1 cells was found to displace endogenous EPAC 1 from the nuclear / perinuclear fraction , thereby inhibiting EPAC activated Rap 1 in this compartment . ^^^ LC 1 , however , was able to enhance interaction of EPAC 1 with cyclic AMP and heightened the ability of EPAC to activate Rap 1 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Indeed , introduction of a constitutively active Rap 1 as well as Epac induces integrin mediated cell adhesion , whereas inhibition of Rap 1 signalling by the introduction of Rap1GAP ( GTPase activating protein ) inhibits inside out activation of integrins . ^^^ More importantly , activation of a G ( s ) protein coupled receptor results in integrin mediated cell adhesion , by a pathway involving Epac and Rap 1 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| We originally noticed that in cells expressing Epac , a cAMP dependent Rap 1 GEF ( guanine nucleotide exchange factor ) , cAMP activated Rap 1 at the perinuclear region , as did EGF . ^^^ Based on the uniform cytoplasmic expression of Epac and e GRF , GEF did not appear to account for the non uniform increase in the activities of Ras and Rap 1 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Neither the Ras exchange factor , Son of sevenless ( SOS ) , nor the cAMP responsive Rap 1 exchange factor , Epac , participate in the cAMP dependent activation of Ras . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Guanine nucleotide exchange factors ( GEFs ) for Rap 1 , C3G , Epac ( or cyclic AMP [ cAMP ] GEF ) , CalDAG GEFI , PDZ GEF 1 , and GFR efficiently increased the level of GTP Rap 2 both in 293T cells and in vitro . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Mutation analysis of the Epac Rap 1 signaling pathway in cold thyroid follicular adenomas . ^^^ DESIGN : Epac and Rap 1 ( Rap1A and Rap1B ) cDNAs were sequenced in 10 patients . ^^^ RESULTS : No mutations in either Epac or Rap 1 cDNAs were found . ^^^ CONCLUSIONS : In this report , we show that the cAMP Epac Rap 1 signaling pathway in the thyroid gland does not play a major role in the generation of cold thyroid follicular adenomas , since no mutations in either Epac or Rap 1 could be observed in the 10 nodules studied . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| The role of Rap 1 in ERK and Akt activity was further demonstrated by our observation that an active form of Epac , which activated Rap 1 in the absence of cAMP , increased ERK and Akt phosphorylation . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Epac belongs to a new family of proteins that can directly mediate the action of the intracellular second messenger cAMP by activating a downstream small GTPase Rap 1 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Although one effector of Epac is the Ras related G protein Rap 1 , it is not fully understood what the functional consequences of Epac mediated signal transduction are at the cellular level . 8 ( 4 chloro phenylthio ) 2 ' O methyladenosine 3 ' 5 ' cyclic monophosphate ( 8 pCPT 2 ' O Me cAMP ) is a newly described cAMP analog , and it activates Epac but not PKA . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Cyclic AMP induces integrin mediated cell adhesion through Epac and Rap 1 upon stimulation of the beta 2 adrenergic receptor . cAMP controls many cellular processes mainly through the activation of protein kinase A ( PKA ) . ^^^ However , more recently PKA independent pathways have been established through the exchange protein directly activated by cAMP ( Epac ) , a guanine nucleotide exchange factor for the small GTPases Rap 1 and Rap 2 . ^^^ In this report , we show that cAMP can induce integrin mediated cell adhesion through Epac and Rap 1 . ^^^ Both the cAMP effect and the Epac effect on cell adhesion were abolished by the expression of Rap 1 GTPase activating protein , indicating the involvement of Rap 1 in the signaling pathway . ^^^ Finally , we demonstrate that external stimuli of cAMP signaling , i . e . , isoproterenol , which activates the G alpha s coupled beta 2 adrenergic receptor can induce integrin mediated cell adhesion through the Epac Rap 1 pathway . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| CAMP activates Rap 1 in differentiating mouse male germ cells : a new signaling pathway mediated by the cAMP activated exchange factor Epac . ^^^ Since cAMP induced Rap 1 activation is actually retained to occur through Epac , we checked whether this recently discovered Rap 1 exchange factor is expressed in male germ cells . ^^^ Taken together , our data show that cAMP activates Rap 1 in differentiating male germ cells which express the cAMP sensor Epac , thus suggesting that this activation might occur directly through Epac . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Effects of GIP on cell survival and inhibition of caspase 3 were mimicked by forskolin , but pharmacological experiments excluded roles for MAPK kinase ( Mek ) 1 / 2 , phosphatidylinositol 3 kinase , protein kinase A , Epac , and Rap 1 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Five years ago , Epac a guanine nucleotide exchange factor for the Ras like small GTPases Rap 1 and Rap 2 was found to be a new target of cyclic AMP , which opened up new avenues for cAMP research . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Activation of Ral was independent of the activation of Epac , a cAMP regulated exchange factor for the small GTPases Rap 1 and Rap 2 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| In contrast , incubation with a cAMP analogue ( 8 ( 4 chloro phenylthio ) 2 ' O methyadenosine 3 ' , 5 ' cyclic monophosphate [ 8CPT 2Me cAMP ] ) that specifically activates the cAMP inducible Rap 1 exchange factor , Epac , did not inhibit SRF . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| On the other hand , Rap 1 activation mediated by two other GEFs , Epac and smgGDS , was not inhibited by Rap 1 AGE . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Our studies suggest that : ( 1 ) the increase in cAMP , induced to differentiate MSCs , activates the classical PKA pathway and not through the exchange protein directly activated by cAMP ( EPAC ) , a guanine nucleotide exchange factor for the small GTPase Rap 1 and Rap 2 ; ( 2 ) MEK ERK signaling could contribute to neural commitment and differentiation ; ( 3 ) CaM KII activity seems dispensable for neuron differentiation . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Cyclic AMP potentiates vascular endothelial cadherin mediated cell cell contact to enhance endothelial barrier function through an Epac Rap 1 signaling pathway . ^^^ Although the decreased permeability and the increased VE cadherin mediated adhesion by prostacyclin and forskolin were insensitive to a specific inhibitor for cAMP dependent protein kinase , these effects were mimicked by 8 ( 4 chlorophenylthio ) 2 ' O methyladenosine 3 ' , 5 ' cyclic monophosphate , a specific activator for Epac , which is a novel cAMP dependent guanine nucleotide exchange factor for Rap 1 . ^^^ In conclusion , cAMP Epac Rap 1 signaling promotes decreased cell permeability by enhancing VE cadherin mediated adhesion lined by the rearranged cortical actin . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| The cAMP dependent exchange factor Epac ( exchange protein directly activated by cAMP ) is a likely upstream activator of Rap 1 , since Epac is present in these cells and the Epac specific cAMP analog 8CPT 2 Me ( 8 ( 4 cholorophenylthio ) 2 ' O methyl cAMP ) activated Rap 1 and promoted SS RBC adhesion to laminin . ^^^ These results demonstrate that Epac induced Rap 1 activation in SS RBCs promotes BCAM / LU mediated adhesion to laminin . ^^^ Thus , Epac mediated Rap 1 activation may represent an important signaling pathway for promoting SS RBC adhesion . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| More importantly , TGF beta 1 greatly reduced the capacity of PMA or chemokines to activate CD11b and Rap 1 , a phenomenon paralleled by a loss of the Epac transcript and a reduction in 8 pCPT 2 ' O Me cAMP mediated activation of Rap 1 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Novel Rap 1 dominant negative mutants interfere selectively with C3G and Epac . ^^^ The lack of potent Rap 1 dominant negative mutants has limited our ability to decipher Rap 1 dependent pathways ; we have therefore developed a procedure to generate such mutants consisting in the oligonucleotide mediated mutagenesis of residues 14 19 , selection of mutants presenting an enhanced interaction with Epac 2 by yeast two hybrid screening and counter screening for mutants still interacting with Rap effectors . ^^^ In cellular models where Rap 1 is activated via endogenous GEFs , the Rap 1 [ S17A ] mutant inhibits both the cAMP Epac and EGF C3G pathways , whereas Rap 1 [ G15D ] selectively interferes with the latter . ^^^ Finally , Rap 1 [ S17A ] is able to act as a bona fide dominant negative mutant in vivo since it phenocopies the eye reducing and lethal effects of D Rap 1 deficiency in Drosophila , effects that are overcome by the overexpression of D Epac or D Rap1 . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Epac 1 mediated Rap 1 activation is not required for the production of nitric oxide in BV 2 , murine microglial cells . ^^^ In contrast , the Epac specific cAMP analog 8 ( 4 chloro phenylthio ) 2 ' O methyladenosine 3 ' , 5 ' cyclic monophosphate ( 8CPT 2Me cAMP ) activates Rap 1 in the BV 2 cells , but does not induce PKA activation , as judged by CREB phosphorylation . ^^^ This suggests that LPS stimulated NO production is mainly PKA dependent and also that Epac 1 mediated Rap 1 activation is not required for the induction of NO production . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Surprisingly , the effect of cAMP was independent of protein kinase A and the exchange protein directly activated by cAMP ( Epac ) Rap 1 pathway and suggests the existence of a novel cAMP dependent mechanism . p 38 MAPK inhibitor SB 203580 , but not extracellular regulated protein kinase inhibitor , abrogated isoproterenol induced IL 6 release in cardiac fibroblasts and mouse myocardium . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| In contrast , components of the PKA independent ( Epac ) pathway , including Rap 1 or B Raf , were not phosphorylated by strain . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| The EPAC specific cyclic AMP analogue , 8 CPT 2Me cAMP was able to activate Rap 1 , but failed to induce growth arrest or induction p27Kip1 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Here we demonstrated that the gating function of GJ is enhanced by the protein kinase A ( PKA ) dependent signal , and that the accumulation of connexin 43 ( Cx 43 ) , the most abundant Cx in myocytes , is enhanced by an exchange protein directly activated by cAMP ( Epac ) ( Rap 1 activator ) dependent signal . ^^^ Because AJ formation precedes the GJ formation , AJ formation accelerated by Epac Rap 1 signal may result in enhanced GJ formation . ^^^ The involvement of Epac Rap 1 signal in GJ neoformation was further confirmed by evidence that inactivation of Rap 1 by overexpression of Rap1GAP1b perturbed the accumulation of Cx 43 at cell cell contacts . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| We have found that EPAC interacts with an ancillary protein , called LC 2 ( light chain 2 ) , and this interaction enhances EPAC ' s ability to activate its substrate protein , Rap 1 GTPase . ^^^ LC 2 appears to enhance EPAC activity towards Rap 1 by increasing the ability of EPAC to interact with cAMP , so that EPAC activation occurs at lower concentrations of cAMP . ^^^ The design of inhibitors that disrupt or enhance EPAC 1 LC2 interaction may therefore form the basis of future therapeutics for diseases where cAMP signalling through Rap 1 is improperly regulated . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Finally , since the cAMP EPAC Rap 1 pathway also activates DARPP 32 ( 32 kDa dopamine response protein phosphatase ) , we confirmed that dopamine phosphorylates DARPP 32 , and okadaic acid , which blocks phosphatases ( DARPP 32 ) , also blocks dopamine ' s effect . ^^^ In summary , dopamine increases ENaC activity by a cAMP mediated alternative signaling pathway involving EPAC and Rap 1 , signaling molecules usually associated with growth factor activated receptors . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Epac proteins ( exchange proteins directly activated by cAMP ) are guanine nucleotide exchange factors ( GEFs ) for the small GTP binding proteins Rap 1 and Rap 2 that are directly regulated by the second messenger cyclic AMP and function in the control of diverse cellular processes , including cell adhesion and insulin secretion . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Differential and brain region specific regulation of Rap 1 and Epac in depressed suicide victims . ^^^ Rap 1 is also activated directly by cyclic adenosine monophosphate through Epac , and thus participates in mediating physiologic functions independent of protein kinase A . ^^^ OBJECTIVE : To examine whether the pathogenesis of depression is associated with altered activation and expression of Rap 1 , as well as expression of Epac , in depressed suicide victims . ^^^ MAIN OUTCOME MEASURES : Rap 1 activation as well as messenger RNA and protein levels of Rap 1 and Epac in prefrontal cortex , hippocampus , and cerebellum . ^^^ CONCLUSION : Given the importance of Rap 1 in neuroprotection and synaptic plasticity , our findings of differential regulation of Rap 1 and Epac between brain regions suggest the relevance of these molecules in the pathophysiology of depression . . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| Interestingly , the inhibition of STAT phosphorylation and SOCS 3 induction did not require cAMP dependent protein kinase activity but could be recapitulated upon selective activation of the alternative cAMP sensor Epac , a guanine nucleotide exchange factor for Rap 1 . ^^^ |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: O95398 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|