Asset Details
Do you wish to reserve the book?
A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
Do you wish to request the book?
A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
A novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
2002
Overview
cAMP is involved in a wide variety of cellular processes that were thought to be mediated by protein kinase A (PKA)
1
. However, cAMP also directly regulates Epac1 and Epac2, guanine nucleotide-exchange factors (GEFs) for the small GTPases Rap1 and Rap2 (refs
2
,
3
). Unfortunately, there is an absence of tools to discriminate between PKA- and Epac-mediated effects. Therefore, through rational drug design we have developed a novel cAMP analogue, 8-(4-chloro-phenylthio)-2′-
O
-methyladenosine-3′,5′-cyclic monophosphate (8CPT-2Me-cAMP), which activates Epac, but not PKA, both
in vitro
and
in vivo
. Using this analogue, we tested the widespread model that Rap1 mediates cAMP-induced regulation of the extracellular signal-regulated kinase (ERK)
4
,
5
. However, both in cell lines in which cAMP inhibits growth-factor-induced ERK activation and in which cAMP activates ERK, 8CPT-2Me-cAMP did not affect ERK activity. Moreover, in cell lines in which cAMP activates ERK, inhibition of PKA and Ras, but not Rap1, abolished cAMP-mediated ERK activation. We conclude that cAMP-induced regulation of ERK and activation of Rap1 are independent processes.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
8-Bromo Cyclic Adenosine Monophosphate - analogs & derivatives
/ 8-Bromo Cyclic Adenosine Monophosphate - metabolism
/ Animals
/ Biomedical and Life Sciences
/ Cyclic AMP-Dependent Protein Kinases - metabolism
/ Dose-Response Relationship, Drug
/ Enzyme Inhibitors - pharmacology
/ Guanine Nucleotide Exchange Factors - metabolism
/ Humans
/ Mice
/ Mitogen-Activated Protein Kinases - metabolism
/ rap1 GTP-Binding Proteins - metabolism
