The regulation of β-adrenergic receptor-mediated PKA activation by substrate stiffness via microtubule dynamics in human MSCs.

ABSTRACT: The mechanical microenvironment surrounding cells has a significant impact on cellular function. One prominent example is that the stiffness of the substrate directs stem cell differentiation. However, the underlying mechanisms of how mechanical cues affect stem cell functions are largely elusive. Here, we report that in human mesenchymal stem cells (HMSCs), substrate stiffness can regulate cellular responses to a β-adrenergic receptor (β-AR) agonist, Isoproterenol (ISO). Fluorescence resonance energy transfer-based A-Kinase Activity Reporter revealed that HMSCs displayed low activity of ISO-induced protein kinase A (PKA) signal on soft substrate, whereas a significantly higher activity can be observed on hard substrate. Meanwhile, there is an increasing ISO-induced internalization of β2-A

SUBMITTER: Kim TJ 

PROVIDER: S-EPMC4144871 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature