Abstract
Activation of the adenylyl cyclase signaling pathway elicits the induction of genes via activators binding to cAMP-responsive elements (CREs). Nuclear factor CRE modulator (CREM) is activated by PKA-mediated phosphorylation on a serine at position 117. We show that Ser-117 is also phosphorylated by the mitogen-activated p70 S6 kinase (p70S6K) in vitro. Activation of cellular p70S6K by serum factors enhances Ser-117 phosphorylation and CREM transactivation. Coexpression of p70S6K significantly increases transactivation by a GAL4-CREM fusion. The macrolide rapamycin, a potent and specific inhibitor of p70S6K in vivo, completely blocks CREM activation induced by serum and by p70S6K. Thus, CREM constitutes a target for mitogenic signaling through p70S6K and may acts as a nuclear effector in which transduction pathways may converge and cross-talk.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Blood Proteins / pharmacology
-
Cell Line
-
Cyclic AMP Response Element Modulator
-
DNA / metabolism
-
DNA, Complementary
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism*
-
Enzyme Activation / drug effects
-
Mitogens / pharmacology
-
Molecular Sequence Data
-
Phosphoproteins / analysis
-
Phosphorylation / drug effects
-
Polyenes / pharmacology
-
Protein Binding
-
Protein Serine-Threonine Kinases / antagonists & inhibitors
-
Protein Serine-Threonine Kinases / genetics
-
Protein Serine-Threonine Kinases / metabolism*
-
Recombinant Fusion Proteins / metabolism
-
Repressor Proteins*
-
Ribosomal Protein S6 Kinases
-
Serine / metabolism
-
Sirolimus
-
Transcriptional Activation / drug effects
-
Transcriptional Activation / physiology*
-
Transfection
-
Up-Regulation*
Substances
-
Blood Proteins
-
DNA, Complementary
-
DNA-Binding Proteins
-
Mitogens
-
Phosphoproteins
-
Polyenes
-
Recombinant Fusion Proteins
-
Repressor Proteins
-
Cyclic AMP Response Element Modulator
-
Serine
-
DNA
-
Protein Serine-Threonine Kinases
-
Ribosomal Protein S6 Kinases
-
Sirolimus