Protein kinase activity of Tel1p and Mec1p, two Saccharomyces cerevisiae proteins related to the human ATM protein kinase

Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13749-54. doi: 10.1073/pnas.250475697.

Abstract

The Saccharomyces cerevisiae proteins Tel1p and Mec1p are involved in telomere length regulation and cellular responses to DNA damage. The closest relative of these proteins is the human Ataxia Telangiectasia Mutated (ATM) protein, a wortmannin-sensitive protein kinase that primarily phosphorylates serines in an SQ motif. We constructed yeast strains containing functional epitope-tagged versions of Tel1p and Mec1p. We showed that immunoprecipitated Tel1p and Mec1p were capable of in vitro phosphorylation of the mammalian protein PHAS-I (Phosphorylated Heat and Acid Stable protein). These activities are sensitive to wortmannin. Tel1p phosphorylates serine in an SQ motif in PHAS-I. Mutations in the kinase domains of Tel1p and Mec1p result in loss of in vitro kinase activity and the in vivo phenotypes associated with the null tel1 and mec1 mutations.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Ataxia Telangiectasia Mutated Proteins
  • Base Sequence
  • Carrier Proteins*
  • Cell Cycle Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • Fungal Proteins / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Tumor Suppressor Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA Primers
  • DNA-Binding Proteins
  • EIF4EBP1 protein, human
  • Fungal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Saccharomyces cerevisiae Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • MEC1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae