Somatostatin receptor 1 (SSTR1)-mediated inhibition of cell proliferation correlates with the activation of the MAP kinase cascade: Role of the phosphotyrosine phosphatase SHP-2

Tullio Florio, Stefano Thellung, Sara Arena, Alessandro Corsaro, Adriana Bajetto, Gennaro Schettini, Philip J.S. Stork

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


The mitogen activated protein (MAP) kinase cascade represents one of the major regulator of cell growth by hormones and growth factors. However, although the activation of this intracellular pathway has been often regarded as mediator of cell proliferation, in many cell types the increase in MAP kinase (also called extra-cellular signal regulated kinase; ERK) activity may result in cell growth arrest, depending on the length or the intensity of the stimulation. In this review we examine recent data concerning the effects of somatostatin on the MAP kinase cascade through one of its major receptor subtype, the somatostatin receptor 1 (SSTR1), stably expressed in CHO-K1 cells. Somatostatin inhibits the proliferative effects of basic FGF (bFGF) in CHO-SSTR1 cell line. However, in these cells, somatostatin robustly activates the MAP kinase and augments bFGF-induced stimulation of ERK. We show that the activation of ERK via SSTR1 is mediated by the βγ subunit of a pertussis toxin-sensitive G-protein and requires both the small G protein Ras and the serine/threonine kinase Raf-1. Moreover the phosphatidyl inositol-3kinase and the cytosolic tyrosine kinase c-src participate in the signal transduction regulated by SSTR1 to activate ERK, as well as it is involved the protein tyrosine phosphatase (PTP) SHP-2. Previous studies have suggested that somatostatin-stimulated PTP activity mediates the growth inhibitory actions of somatostatin, in CHO-SSTR1 cells. Thus, the activation of SHP-2 by SSTR1 may mediate the antiproliferative activity of somatostatin. SHP-2 may, in turn, regulate the activity of kinases upstream of ERK that require tyrosine dephosphorylation to be activated, such as c-src. Finally, the synergism between somatostatin and bFGF in the activation of ERK results in an increased expression of the cyclin-dependent kinase inhibitor p21(cip1/WAF1) as molecular effector of the antiproliferative activity of somatostatin. (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)239-250
Number of pages12
JournalJournal of Physiology Paris
Issue number3-4
StatePublished - 2000


  • Cell proliferation
  • Map kinase
  • Somatostatin
  • Tyrosine phosphatase
  • p21(cip1/WAF1)

ASJC Scopus subject areas

  • General Neuroscience
  • Physiology (medical)


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