Crosstalk between signaling pathways of adrenoreceptors and signal transducers and activators of transcription 3 (STAT3) in heart
Abstract
Recently, there have been important advancements in our understanding of the
signaling mechanisms of adrenoreceptors (AR) and signal transducers and activators
of transcription 3 (STAT3). While their crucial roles in the pathological
processes of the heart are well established, accumulating evidence suggests there
is a complex pattern of crosstalk between these 2 signaling pathways. Moreover,
the potential for crosstalk occurs at multiple levels in each signaling cascade and
involves receptor transactivation, G proteins, small GTPases, cyclic adenosine 3',
5'-monophosphate/protein kinase A, protein kinase C, scaffold/adaptor proteins,
protein tyrosine kinases, and mitogen-activated protein kinases. In addition, posttranslational
modification (eg acetylation) of STAT3 may provide a link between
STAT3 and AR signaling. In particular, crosstalk between these 2 systems in the
heart would appear to be dependent upon the species/tissue studied, developmental
stage, and eliciting stimulus. This at least partly accounts for the epigenetic
effects on biological function that is mediated by the 2 signaling pathways.
Elucidation of these mechanisms will provide new targets in the development of
novel clinical strategies for heart disorders.
Keywords:
signaling mechanisms of adrenoreceptors (AR) and signal transducers and activators
of transcription 3 (STAT3). While their crucial roles in the pathological
processes of the heart are well established, accumulating evidence suggests there
is a complex pattern of crosstalk between these 2 signaling pathways. Moreover,
the potential for crosstalk occurs at multiple levels in each signaling cascade and
involves receptor transactivation, G proteins, small GTPases, cyclic adenosine 3',
5'-monophosphate/protein kinase A, protein kinase C, scaffold/adaptor proteins,
protein tyrosine kinases, and mitogen-activated protein kinases. In addition, posttranslational
modification (eg acetylation) of STAT3 may provide a link between
STAT3 and AR signaling. In particular, crosstalk between these 2 systems in the
heart would appear to be dependent upon the species/tissue studied, developmental
stage, and eliciting stimulus. This at least partly accounts for the epigenetic
effects on biological function that is mediated by the 2 signaling pathways.
Elucidation of these mechanisms will provide new targets in the development of
novel clinical strategies for heart disorders.