Sphingosine 1-phosphate-mediated α1B-adrenoceptor desensitization and phosphorylation. Direct and paracrine/autocrine actions

Biochim Biophys Acta. 2012 Feb;1823(2):245-54. doi: 10.1016/j.bbamcr.2011.10.002. Epub 2011 Oct 13.


Sphingosine-1-phosphate-induced α1B-adrenergic receptor desensitization and phosphorylation were studied in rat-1 fibroblasts stably expressing enhanced green fluorescent protein-tagged adrenoceptors. Sphingosine-1-phosphate induced adrenoceptor desensitization and phosphorylation through a signaling cascade that involved phosphoinositide 3-kinase and protein kinase C activities. The autocrine/paracrine role of sphingosine-1-phosphate was also studied. It was observed that activation of receptor tyrosine kinases, such as insulin growth factor-1 (IGF-I) and epidermal growth factor (EGF) receptors increased sphingosine kinase activity. Such activation and consequent production of sphingosine-1-phosphate appear to be functionally relevant in IGF-I- and EGF-induced α1B-adrenoceptor phosphorylation and desensitization as evidenced by the following facts: a) expression of a catalytically inactive (dominant-negative) mutant of sphingosine kinase 1 or b) S1P1 receptor knockdown markedly reduced this growth factor action. This action of sphingosine-1-phosphate involves EGF receptor transactivation. In addition, taking advantage of the presence of the eGFP tag in the receptor construction, we showed that S1P was capable of inducing α1B-adrenergic receptor internalization and that its autocrine/paracrine generation was relevant for internalization induced by IGF-I. Four distinct hormone receptors and two autocrine/paracrine mediators participate in IGF-I receptor-α1B-adrenergic receptor crosstalk.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication / physiology*
  • ErbB Receptors / antagonists & inhibitors
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Humans
  • Lysophospholipids / metabolism*
  • Paracrine Communication / physiology*
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Rats
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Receptors, Lysosphingolipid / genetics
  • Receptors, Lysosphingolipid / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / metabolism


  • ADRA1B protein, human
  • Lysophospholipids
  • Receptors, Adrenergic, alpha-1
  • Receptors, Lysosphingolipid
  • sphingosine 1-phosphate
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • ErbB Receptors
  • Receptor, IGF Type 1
  • Sphingosine