title: Catalytic domains of tyrosine kinases determine the phosphorylation sites within c-Cbl.
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.
authors.affiliation: Department of Hematology & Medical Oncology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, L592 Portland, OR 97239, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Grossmann
authors.forename: K S
authors.initials: KS
authors.lastname: Kolibaba
authors.forename: S G
authors.initials: SG
authors.lastname: Willis
authors.forename: A S
authors.initials: AS
authors.lastname: Corbin
authors.forename: W S
authors.initials: WS
authors.lastname: Langdon
authors.forename: M W N
authors.initials: MW
authors.lastname: Deininger
authors.forename: B J
authors.initials: BJ
authors.lastname: Druker
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000235:genetics; D005982:Glutathione Transferase / Q000378:metabolism; D015151:Immunoblotting; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014443:Tyrosine / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases