p85 subunit of PI3 kinase does not bind to human Flt3 receptor, but associates with SHP2, SHIP, and a tyrosine-phosphorylated 100-kDa protein in Flt3 ligand-stimulated hematopoietic cells.
Flt3/Flk2 belongs to class III receptor tyrosine kinases. Like other members of type III receptor tyrosine kinases, murine Flt3 induces tyrosine phosphorylation of p85 and subsequently activation of PI3 kinase upon FL binding. While p85 binds murine Flt3 at Y958 in the carboxyl terminus of the receptor, human Flt3 does ... not have a potential p85-binding site in the carboxyl terminus. In this study, we examined whether p85 binds to human Flt3 in Baf3/Flt3 and THP-1 cells. In contrast to murine Flt3, p85 is not tyrosine phosphorylated after FL stimulation, nor does it bind Flt3 in both cell lines. Instead p85 associates inducibly with tyrosine phosphorylated SHP-2 and constitutively with SHIP and two tyrosine phosphorylated proteins with molecular weights about 100-kDa (p100) and 120-kDa (p120) in Baf3/Flt3 cells. The p100 associates with both p85 and SHP-2. In THP-1 cells, p85 associates inducibly with tyrosine phosphorylated SHIP, p100 and p120. These results indicate that p85 does not bind human Flt3, but forms a complex with SHP-2, SHIP, p100 and p120 in hematopoietic cells.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Amino Acid Sequence, Animals, Binding Sites, Cell Line, Hematopoietic Stem Cells, Humans, Intracellular Signaling Peptides and Proteins, Macromolecular Substances, Mice, Molecular Sequence Data, Phosphoric Monoester Hydrolases, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Receptors, Cell Surface, Recombinant Proteins, SH2 Domain-Containing Protein Tyrosine Phosphatases, Sequence Alignment, Sequence Homology, Amino Acid, Transfection, fms-Like Tyrosine Kinase 3, src Homology Domains
1-Phosphatidylinositol 3-Kinase, Amino Acid Sequence, Animals, Binding Sites, Cell Line, Hematopoietic Stem Cells, Humans, Intracellular Signaling Peptides and Proteins, Macromolecular Substances, Mice, Molecular Sequence Data, Phosphoric Monoester Hydrolases, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Receptors, Cell Surface, Recombinant Proteins, SH2 Domain-Containing Protein Tyrosine Phosphatases, Sequence Alignment, Sequence Homology, Amino Acid, Transfection, fms-Like Tyrosine Kinase 3, src Homology Domains
Biochem. Biophys. Res. Commun.
Date: Jan. 19, 1999
PubMed ID: 9918857
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