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Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body

S Felder1, K Miller, G Moehren

  • 1Rorer Biotechnology, Inc., King of Prussia, Pennsylvania 19406.

Cell
|May 18, 1990
PubMed

Insights

Kinase-negative epidermal growth factor receptor (EGF-R) recycles, unlike wild-type EGF-R. Receptor sorting for degradation or recycling is controlled by tyrosine kinase activity and occurs within multivesicular bodies.

Area of Science:

  • Cell biology
  • Molecular signaling
  • Receptor trafficking

Background:

  • Epidermal growth factor receptor (EGF-R) signaling is crucial for cell growth and differentiation.
  • Understanding EGF-R internalization and intracellular sorting is key to deciphering its role in cellular processes.
  • Dysregulation of EGF-R is implicated in various cancers.

Purpose of the Study:

  • To compare the internalization and intracellular sorting of wild-type EGF-R and a kinase-negative mutant.
  • To investigate the role of tyrosine kinase activity in EGF-R sorting and trafficking.
  • To elucidate the mechanisms governing EGF-R degradation versus recycling.

Main Methods:

  • Expression of wild-type and kinase-negative EGF-R in NIH 3T3 cells.
  • Analysis of EGF-R internalization and surface down-regulation under various conditions (monensin, temperature).
  • Electron microscopy to visualize intracellular pathways and localization within multivesicular bodies (MVBs).

Main Results:

  • Both wild-type and kinase-negative EGF-Rs internalized rapidly.
  • Kinase-negative EGF-R showed reduced surface down-regulation and significant recycling of internalized EGF.
  • Electron microscopy revealed divergent intracellular pathways at the MVB stage, with wild-type EGF-R targeted for degradation and kinase-negative EGF-R for recycling.

Conclusions:

  • EGF-R sorting for degradation or recycling is spatially segregated within the MVB.
  • Tyrosine kinase activity of EGF-R is a critical determinant of its intracellular sorting fate.
  • Kinase-inactive EGF-R exhibits a distinct recycling pathway compared to wild-type EGF-R.

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