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Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
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Published on: July 17, 2020

SHP-2 regulates growth factor dependent vascular signalling and function.

Hanna Mannell, Florian Krotz1

  • 1Invasive Cardiology, Clinic Starnberg, Oßwaldstr. 1, 82319 Munich, Germany. floriankroetz@gmx.de.

Mini Reviews in Medicinal Chemistry
|April 20, 2012
PubMed
Summary

The protein tyrosine phosphatase SHP-2 regulates key cellular processes, including proliferation and survival. Dysregulation of SHP-2 is linked to vascular disorders and malignancies, highlighting its critical role in cell signaling.

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Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Vascular Biology

Background:

  • Intracellular signaling pathways control cellular functions like proliferation, migration, differentiation, and survival.
  • Dysregulation of these pathways leads to cellular dysfunction and pathophysiological conditions.
  • SHP-2 (non-transmembrane protein tyrosine phosphatase) is crucial for regulating cellular behavior and signaling pathways.

Purpose of the Study:

  • To summarize the role of SHP-2 in signaling pathways relevant to vascular biology.
  • To explore SHP-2's involvement in cellular processes and associated disorders.
  • To highlight SHP-2's impact on endothelial cell function and angiogenesis.

Main Methods:

  • Literature review and summary of existing research on SHP-2 function.
  • Analysis of SHP-2's interactions with growth factor receptors and adaptor molecules (Gab-1, Grb2, IRS-1).
  • Examination of SHP-2's role in MAPK and PI3-K/Akt pathways.

Main Results:

  • SHP-2 regulates MAPK pathway activation upon stimulation by FGF-2, EGF, and insulin.
  • SHP-2 influences cell survival via the PI3-K/Akt pathway upon EGF, IGF, and PDGF stimulation.
  • SHP-2 positively regulates endothelial cell motility and angiogenesis, but also down-regulates VEGF receptor 2 activation.

Conclusions:

  • SHP-2 plays a significant role in vascular processes, including cardiac progenitor cell differentiation and angiogenesis.
  • Mutations in the Ptpn11 gene (encoding SHP-2) are associated with developmental disorders (Noonan, Leopard syndromes) and malignancies.
  • SHP-2 is a key regulator in signaling pathways critical for vascular health and disease.