Document Type

Article

Publication Date

2002

Abstract

In fibrolast cells, cAMP antagonizes growth factor activation of ERKs and cell growth via PKA and the small P 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 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.

Comments

Originally published in Molecular Cell, Vol. 9, 85–94, January 2002.

https://doi.org/10.1016/S1097-2765(01)00432-4

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