title: PKA phosphorylation of Src mediates cAMP's inhibition of cell growth via Rap1.
abstract: In fibroblast cells, cAMP antagonizes growth factor activation of ERKs and cell growth via PKA and the small G protein Rap1. We demonstrate here that PKA's activation of Rap1 was mediated by the Rap1 guanine nucleotide exchange factor C3G, the adaptor Crk-L, the scaffold protein Cbl, and the tyrosine kinase Src. Src was required for cAMP activation of Rap1 and the inhibition of ERKs and cell growth. PKA activated Src both in vitro and in vivo by phosphorylating Src on serine 17 within its amino terminus. This phosphorylation was required for cAMP's activation of Src and Rap1, as well as cAMP's inhibition of ERKs and cell proliferation. This study identifies an antiproliferative role for Src in the physiological regulation of cell growth by cAMP.
authors.affiliation: Vollum Institute and Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland, OR 97201, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Schmitt
authors.forename: Philip J S
authors.initials: PJ
authors.lastname: Stork
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D051379:Mice; D010766:Phosphorylation; D015398:Signal Transduction; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000242:Cyclic AMP; D019061:src-Family Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D020827:rap1 GTP-Binding Proteins