2. Academic Validation
  3. Catalytic domains of tyrosine kinases determine the phosphorylation sites within c-Cbl

Catalytic domains of tyrosine kinases determine the phosphorylation sites within c-Cbl

  • FEBS Lett. 2004 Nov 19;577(3):555-62. doi: 10.1016/j.febslet.2004.10.054.
A H Grossmann 1,  K S Kolibaba,  S G Willis,  A S Corbin,  W S Langdon,  M W N Deininger,  B J Druker
Affiliations

Affiliation

  • 1 Department of Hematology & Medical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, L592 Portland, OR 97239, USA.
PMID: 15556646 DOI: 10.1016/j.febslet.2004.10.054
Abstract

Catalytic (SH1) domains of Protein Tyrosine Kinases (PTKs) demonstrate specificity for peptide substrates. Whether SH1 domains differentiate between tyrosines in a physiological substrate has not been confirmed. Using purified proteins, we studied the ability of Syk, Fyn, and Abl to differentiate between tyrosines in a common PTK substrate, c-Cbl. We found that each kinase produced a distinct pattern of c-Cbl phosphorylation, which altered the phosphotyrosine-dependent interactions between c-Cbl and CrkL or phosphatidylinositol 3'-kinase (PI3-K). Our data support the concept that SH1 domains determine the final sites of phosphorylation once PTKs reach their target proteins.

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