Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of the microtubule-disruptive agent, nocodazole (methyl [5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl] carbamate), on the water permeability response to vasopressin or the synthetic cyclic AMP analogue, 8-parachlorophenylthio-cyclic AMP (8-CPT-cAMP), has been investigated in isolated cortical collecting tubules from rabbit kidneys, perfused in vitro. 2. Pre-treatment with nocodazole, 1-4 micrograms ml-1, had no significant effect on basal water permeability, but inhibited the increase in hydraulic conductivity elicited by vasopressin, 50 microU ml-1, in a dose-dependent manner. Inhibition of the response to the hormone averaged 65 +/- 6% (n = 8, P less than 0.001) at a nocodazole concentration of 4 micrograms ml-1. 3. Nocodazole, 1-4 micrograms ml-1, had no effect on the increase in lumen-negative potential difference (PD) induced by the hormone. 4. Pre-treatment with nocodazole, 4 micrograms ml-1, inhibited the development of the water permeability response to 8-CPT-cAMP, 1.8 x 10(-5) M, by 45 +/- 7% (n = 7, P less than 0.001). 5. When collecting tubules were exposed to nocodazole, 4 micrograms ml-1, after the hydrosmotic response to vasopressin had been fully established, the drug had no inhibitory effect on the maintenance of a high water permeability. 6. The results are consistent with the view that cytoplasmic microtubules play a role in the initiation of the water permeability response to vasopressin in the mammalian cortical collecting tubule at a cellular site beyond the generation of cyclic AMP.
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PMID:Effect of nocodazole on the water permeability response to vasopressin in rabbit collecting tubules perfused in vitro. 255 98

We have recently demonstrated that light chain 2 (LC2) of the microtubule-associated protein MAP1A interacts with the cyclic AMP (cAMP)-binding domain of exchange protein directly activated by cyclic AMP 1 (EPAC1). In the present study we used a simultaneous expression system and found that LC2 enhances both basal and 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3':5'-cyclic monophosphate (8-CPT-2Me-cAMP)-stimulated Rap1 activation by EPAC1. LC2 is known to stabilize microtubules; therefore we examined whether microtubules enhanced Rap1 activation by LC2. Nocodazole inhibited Rap1 activity in cells transfected with EPAC1 alone but had little effect on Rap1 activity in cells transfected with both EPAC1 and LC2. This indicates that part of the actions of LC2 in enhancing EPAC1 activity may be through stabilization of microtubules. We also found that in cells transfected with LC2, Rap1 was more sensitive to activation by 8-CPT-2Me-cAMP. Moreover, LC2 enhanced the ability of transfected and endogenous EPAC1 to interact with cyclic AMP-agarose, indicating that LC2 elicits conformational changes in the cAMP domain of EPAC1, enhancing its ability to be activated by cyclic AMP. We also found that disruption of the interaction of endogenous EPAC1 and LC2 with antibodies to the cAMP domain of EPAC1 abolished Rap1 activity in PC12 cell lysates, demonstrating the importance of LC2 for EPAC1 activation in these cells. Consistent with a role of EPAC1 in controlling integrin activity, we found that cell adhesion to laminin was enhanced in LC2- and EPAC1-transfected cells stimulated with 8-CPT-2Me-cAMP. LC2 is therefore a biological enhancer of EPAC1 activity toward Rap1 and associated downstream signaling mechanisms.
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PMID:MAP1A light chain 2 interacts with exchange protein activated by cyclic AMP 1 (EPAC1) to enhance Rap1 GTPase activity and cell adhesion. 1559 Oct 41