A dynamic interface between ubiquitylation and cAMP signaling

Frontiers in Pharmacology

Maria eSepe¹  Laura eRinaldi¹  Rossella eDelle Donne¹  Antonio eFeliciello¹ 

[1] University Federico II;

关键词: Cyclic AMP;    Ubiquitination;    Proteasome;    AKAP;    PKA signaling;   

DOI  :  10.3389/fphar.2015.00177

来源: DOAJ

【 摘 要 】

Phosphorylation waves drive the propagation of signals generated in response to hormones and growth factors in target cells.cAMP is an ancient second messenger implicated in key biological functions. In mammals, most of the effects elicited by cAMP are mediated by protein kinase A (PKA). Activation of the kinase by cAMP results in the phosphorylation of a variety of cellular substrates, leading to differentiation, proliferation, survival, metabolism. The identification of scaffold proteins, namely A-Kinase Anchor proteins (AKAPs), that localize PKA in specific cellular districts, provides critical cues for our understanding of the role played by cAMP in cell biology. Multivalent complexes are assembled by AKAPsand include signaling enzymes, mRNAs, adapter molecules, receptors and ion channels. A novel development derived from the molecular analysis of these complexes nucleated by AKAPs is represented by the presence of components of the ubiquitin proteasome system (UPS). More to it, the AKAP complex can be regulated by the UPS, eliciting relevant effects on downstream cAMP signals.This represents a novel, yet previously unpredicted interface between compartmentalized signaling and the UPS. We anticipate that impairment of these regulatory mechanisms could promote cell dysfunction and disease. Here, we will focus on the reciprocal regulation between cAMP signaling and UPS, and its relevance to human proliferative disorders.

【 授权许可】

Unknown