PIP3 induces the recycling of receptor tyrosine kinases

Vibor Laketa, Sirus Zarbakhsh, Alexis Traynor-Kaplan, Aidan MacNamara, Devaraj Subramanian, Mateusz Putyrski, Rainer Mueller, André Nadler, Matthias Mentel, Julio Saez-Rodriguez, Rainer Pepperkok, Carsten Schultz

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Down-regulation of receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR) is achieved by endocytosis of the receptor followed by degradation or recycling. We demonstrated that in the absence of ligand, increased phosphatidylinositol 3,4,5-trisphosphate (PIP3) concentrations induced clathrin- and dynamin-mediated endocytosis of EGFR but not that of transferrin or G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors. Endocytosis of the receptor in response to binding of EGF resulted in a decrease in the abundance of the EGFR, but PIP 3-induced internalization decreased receptor ubiquitination and phosphorylation and resulted in recycling of the receptor to the plasma membrane. An RNA interference (RNAi) screen directed against lipid-binding domain-containing proteins identified polarity complex proteins, including PARD3 (partitioning defective 3), as essential for PIP3-induced receptor tyrosine kinase recycling. Thus, PIP3 and polarity complex proteins regulate receptor tyrosine kinase trafficking, which may enhance cellular responsiveness to growth factors.

Original languageEnglish (US)
Article numberra5
JournalScience Signaling
Volume7
Issue number308
DOIs
StatePublished - Jan 14 2014
Externally publishedYes

Fingerprint

Receptor Protein-Tyrosine Kinases
Endocytosis
Epidermal Growth Factor Receptor
Recycling
Dynamins
Heterotrimeric GTP-Binding Proteins
Clathrin
Phosphorylation
Proteins
Guanine Nucleotides
Ubiquitination
Cell membranes
Transferrin
RNA Interference
Epidermal Growth Factor
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Down-Regulation
Cell Membrane
RNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Laketa, V., Zarbakhsh, S., Traynor-Kaplan, A., MacNamara, A., Subramanian, D., Putyrski, M., ... Schultz, C. (2014). PIP3 induces the recycling of receptor tyrosine kinases. Science Signaling, 7(308), [ra5]. https://doi.org/10.1126/scisignal.2004532

PIP3 induces the recycling of receptor tyrosine kinases. / Laketa, Vibor; Zarbakhsh, Sirus; Traynor-Kaplan, Alexis; MacNamara, Aidan; Subramanian, Devaraj; Putyrski, Mateusz; Mueller, Rainer; Nadler, André; Mentel, Matthias; Saez-Rodriguez, Julio; Pepperkok, Rainer; Schultz, Carsten.

In: Science Signaling, Vol. 7, No. 308, ra5, 14.01.2014.

Research output: Contribution to journalArticle

Laketa, V, Zarbakhsh, S, Traynor-Kaplan, A, MacNamara, A, Subramanian, D, Putyrski, M, Mueller, R, Nadler, A, Mentel, M, Saez-Rodriguez, J, Pepperkok, R & Schultz, C 2014, 'PIP3 induces the recycling of receptor tyrosine kinases', Science Signaling, vol. 7, no. 308, ra5. https://doi.org/10.1126/scisignal.2004532
Laketa V, Zarbakhsh S, Traynor-Kaplan A, MacNamara A, Subramanian D, Putyrski M et al. PIP3 induces the recycling of receptor tyrosine kinases. Science Signaling. 2014 Jan 14;7(308). ra5. https://doi.org/10.1126/scisignal.2004532
Laketa, Vibor ; Zarbakhsh, Sirus ; Traynor-Kaplan, Alexis ; MacNamara, Aidan ; Subramanian, Devaraj ; Putyrski, Mateusz ; Mueller, Rainer ; Nadler, André ; Mentel, Matthias ; Saez-Rodriguez, Julio ; Pepperkok, Rainer ; Schultz, Carsten. / PIP3 induces the recycling of receptor tyrosine kinases. In: Science Signaling. 2014 ; Vol. 7, No. 308.
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