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Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
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A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective

Jason J Kwon1,2,3, William C Hahn4,2,3,5

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Molecular and Cellular Biology
|February 2, 2021
PubMed

Insights

SHOC2 protein is crucial for receptor tyrosine kinase (RTK)/RAS signaling and cellular development. Its mutations cause Noonan-like syndrome, and it confers resistance to MAPK inhibitors, highlighting its role in disease and therapy.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Structural Biology

Background:

  • SHOC2 is a leucine-rich repeat protein involved in receptor tyrosine kinase (RTK)/RAS signaling.
  • Gain-of-function mutations in SHOC2 cause Noonan-like syndrome, a RASopathy.
  • SHOC2 plays a role in adaptive resistance to mitogen-activated protein kinase (MAPK) inhibitors.

Purpose of the Study:

  • To review the structural features of SHOC2 that mediate its functions.
  • To discuss SHOC2's structural elements in the context of binding partners and signaling pathways.
  • To identify areas of SHOC2 biology lacking a consensus view.

Main Methods:

  • Literature review of structural and functional studies on SHOC2.
  • Analysis of SHOC2's role in RTK/RAS and MAPK signaling pathways.
  • Examination of SHOC2's involvement in genetic disorders and drug resistance.

Main Results:

  • SHOC2 acts as a scaffolding protein, facilitating proximal protein interactions and regulating subcellular localization.
  • Structural features of SHOC2 are key to its function in signal transduction.
  • SHOC2's role in RASopathies and MAPK inhibitor resistance is linked to its scaffolding capabilities.

Conclusions:

  • SHOC2's structural characteristics underpin its critical roles in cellular signaling, development, and disease.
  • Understanding SHOC2 structure-function relationships is essential for deciphering its involvement in RASopathies and therapeutic resistance.
  • Further research is needed to resolve outstanding questions in SHOC2 biology.
Keywords:
MAPK signalingNoonan syndromePP1CRAFRASSHOC2cancerleucine-rich repeatreceptor tyrosine kinase

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