Protein kinase A inhibitor proteins (PKIs) divert GPCR-Gαs-cAMP signaling toward EPAC and ERK activation and are involved in tumor growth.

ABSTRACT: The PKA-inhibitor (PKI) family members PKIα, PKIβ, and PKIγ bind with high affinity to PKA and block its kinase activity, modulating the extent, and duration of PKA-mediated signaling events. While PKA is a well-known regulator of physiological and oncogenic events, the role of PKI proteins in these pathways has remained elusive. Here, by measuring activation of the MAPK pathway downstream of GPCR-Gαs-cAMP signaling, we show that the expression levels of PKI proteins can alter the balance of activation of two major cAMP targets: PKA and EPAC. Our results indicate that PKA maintains repressive control over MAPK signaling as well as a negative feedback on cAMP concentration. Overexpression of PKI and its subsequent repression of PKA dysregulates these signaling pathways, resulting in increas

SUBMITTER: Hoy JJ 

PROVIDER: S-EPMC7722164 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature