Detection of Early Abl Kinase Activation after Ionizing Radiation by Using a Peptide Biosensor

Jiabin Tang, Jean Y. Wang, Laurie L. Parker

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The ubiquitously expressed Abl protein is a non-receptor tyrosine kinase that undergoes nuclear-cytoplasmic shuttling and is involved in many signaling pathways in the cell. Nuclear Abl is activated by DNA damage to regulate DNA repair, cell-cycle checkpoints and apoptosis. Previous studies have established that ataxia telangiectasia mutated (ATM) activates nuclear Abl by phosphorylating serine 465 (S465) in the kinase domain in response to ionizing radiation (IR). Using a peptide biosensor that specifically reports on the Abl kinase activity, we found that an Abl-S465A mutant, which is not capable of being activated by ATM through the canonical site, was still activated rapidly after IR. We established that DNA-dependent protein kinase (DNAPK) is likely to be responsible for a second pathway to activate Abl early on in the response to IR through phosphorylation at a site other than S465. Our findings show that nuclear and cytoplasmic Abl kinase is activated early on (within 5 min) in response to IR by both ATM and DNAPK, and that although one or the other of these kinases is required, either one is sufficient to activate Abl. These results support the concept of early Abl recruitment by both the ATM and the DNAPK pathways to regulate nuclear events triggered by DNA damage and potentially communicate them to proteins in the cytoplasm.

Original languageEnglish (US)
Pages (from-to)665-673
Number of pages9
JournalChemBioChem
Volume13
Issue number5
DOIs
StatePublished - Mar 1 2012

Fingerprint

Ataxia Telangiectasia
Ionizing radiation
Biosensing Techniques
DNA-Activated Protein Kinase
Ionizing Radiation
Biosensors
Phosphotransferases
Chemical activation
Peptides
Serine
DNA Damage
DNA
Phosphorylation
Cell Cycle Checkpoints
DNA Repair
Protein-Tyrosine Kinases
Cytoplasm
Proteins
Repair
Cells

Keywords

  • Abl
  • Biosensors
  • DNA damage response
  • Kinases
  • Peptides

Cite this

Detection of Early Abl Kinase Activation after Ionizing Radiation by Using a Peptide Biosensor. / Tang, Jiabin; Wang, Jean Y.; Parker, Laurie L.

In: ChemBioChem, Vol. 13, No. 5, 01.03.2012, p. 665-673.

Research output: Contribution to journalArticle

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