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- Title
14-3-3 binding to the IGF-1 receptor is mediated by serine autophosphorylation<sup>1</sup><FN ID="FN1"><NO>1</NO>This paper is dedicated to Prof. Dr. Ernst J.M. Helmreich on the occasion of his 80th birthday.</FN>
- Authors
Parvaresch, Susan; Yesilkaya, Tanju; Baer, Kristin; Al-Hasani, Hadi; Klein, Helmut W.
- Abstract
The phosphoserine-binding 14-3-3 proteins have been implicated in playing a role in mitogenic and apoptotic signaling pathways. Binding of 14-3-3 proteins to phosphoserine residues in the C-terminus of the insulin-like growth factor-1 receptor (IGF-1R) has been described to occur in a variety of cell systems, but the kinase responsible for this serine phosphorylation has not been identified yet. Here we present evidence that the isolated dimeric insulin-like growth factor-1 receptor kinase domain (IGFKD) contains a dual specific (i.e. tyrosine/serine) kinase activity that mediates autophosphorylation of C-terminal serine residues in the enzyme. From the total phosphate incorporation of ∼4 mol per mol kinase subunit, 1 mol accounts for serine phosphate. However, tyrosine autophosphorylation proceeds more rapidly than autophosphorylation of serine residues (t1/2∼1 min vs. t1/2∼5 min). Moreover, dot-blot and far-Western analyses reveal that serine autophosphorylation of IGFKD is sufficient to promote binding of 14-3-3 proteins in vitro. The proof that dual kinase activity of IGFKD is necessary and sufficient for 14-3-3 binding was obtained with an inactive kinase mutant that was phosphorylated on serine residues in a stoichiometric reaction with the catalytically active enzyme. Thus, the IGF-1R itself might be responsible for the serine autophosphorylation which leads to recognition of 14-3-3 proteins in vivo.
- Subjects
PHOSPHORYLATION; SERINE; PROTEIN binding
- Publication
FEBS Letters, 2002, Vol 532, Issue 3, p357
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/S0014-5793(02)03708-0