Evidence that dynamin-2 functions as a signal-transducing GTPase

Kenneth N. Fish, Sandra L. Schmid, Hanna Damke

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

The role of dynamin GTPases in the regulation of receptor-mediated endocytosis is well established. Here, we present new evidence that the ubiquitously expressed isoform dynamin-2 (dyn2) can also function in a signal transduction pathway(s). A ≤5-fold increase of dyn2 relative to endogenous levels activates the transcription factor p53 and induces apoptosis, as demonstrated by reduced cell proliferation, DNA fragmentation, and caspase-3 activation. Dyn2-triggered apoptosis occurs only in dividing cells and is p53 dependent. A mutant defective in GTP binding does not trigger apoptosis, indicating that increased levels of dyn2·GTP, rather than protein levels per se, are required to transduce signals that activate p53. A truncated dyn2 lacking the COOH-terminal proline/arginine-rich domain (PRD), which interacts with many SH3 domain-containing partners implicated in both endocytosis and signal transduction, triggers apoptosis even more potently than the wild- type. This observation provides additional support for the importance of the NH2-terminal GTPase domain for the apoptotic phenotype. All described effects are dyn2-specific because >200-fold overexpression of dyn1, the 70% identical neuronal isoform, has no effect. Our data suggest that dyn2 can act as a signal transducing GTPase affecting transcriptional regulation.

Original languageEnglish (US)
Pages (from-to)145-154
Number of pages10
JournalJournal of Cell Biology
Volume150
Issue number1
DOIs
StatePublished - Jul 10 2000

Fingerprint

Dynamin II
GTP Phosphohydrolases
Apoptosis
Endocytosis
Signal Transduction
Protein Isoforms
Dynamins
src Homology Domains
DNA Fragmentation
Guanosine Triphosphate
Proline
Caspase 3
Arginine
Transcription Factors
Cell Proliferation
Phenotype
Proteins

Keywords

  • Apoptosis
  • Dynamin
  • Endocytosis
  • GTPase
  • p53

ASJC Scopus subject areas

  • Cell Biology

Cite this

Evidence that dynamin-2 functions as a signal-transducing GTPase. / Fish, Kenneth N.; Schmid, Sandra L.; Damke, Hanna.

In: Journal of Cell Biology, Vol. 150, No. 1, 10.07.2000, p. 145-154.

Research output: Contribution to journalArticle

Fish, Kenneth N. ; Schmid, Sandra L. ; Damke, Hanna. / Evidence that dynamin-2 functions as a signal-transducing GTPase. In: Journal of Cell Biology. 2000 ; Vol. 150, No. 1. pp. 145-154.
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