p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity

Genes Dev. 1996 May 1;10(9):1084-95. doi: 10.1101/gad.10.9.1084.


The production, survival, and function of monocytes and macrophages is regulated by the macrophage colony-stimulating factor (M-CSF or CSF-1) through its tyrosine kinase receptor Fms. Binding of M-CSF to Fms induces the tyrosine phosphorylation and association of a 150-kD protein with the phosphotyrosine-binding (PTB) domain of Shc. We have cloned p150 using a modified yeast two-hybrid screen. p150 contains one SH2 domain, two potential PTB-binding sites, an ATP/GTP-binding domain, several potential SH3-binding sites, and a domain with homology to inositol polyphosphate-5-phosphatases. p150 antibodies detect this protein in FDC-P1 myeloid cells, but the same protein is not detectable in fibroblasts. The antibodies immunoprecipitate a 150-kD protein from quiescent or M-CSF-stimulated FDC-P1 cells that hydrolyzes PtdIns(3,4,5)P3, to PtdIns(3,4)P2. This activity is observed in Shc immunoprecipitates only after M-CSF stimulation. Retroviral expression of p15O in FD-Fms cells results in strong inhibition of cell growth in M-CSF and a lesser inhibition in IL-3. Ectopic expression of p150 in fibroblasts does not inhibit growth. This novel protein, p150(ship) (SH2-containing inositol phosphatase), identifies a component of a new growth factor-receptor signaling pathway in hematopoietic cells.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • DNA, Complementary / genetics
  • Hematopoietic Stem Cells / drug effects
  • Inositol Polyphosphate 5-Phosphatases
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Mice
  • Molecular Sequence Data
  • Organophosphates / pharmacology
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • Phosphoric Monoester Hydrolases / analysis
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphotyrosine / metabolism
  • Protein Binding
  • Proteins / genetics
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Growth Factor / physiology
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Shc Signaling Adaptor Proteins
  • Signal Transduction / physiology*
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Vascular Endothelial Growth Factor Receptor-1
  • src Homology Domains


  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • DNA, Complementary
  • Organophosphates
  • Proteins
  • Proto-Oncogene Proteins
  • Receptors, Growth Factor
  • Recombinant Fusion Proteins
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Phosphotyrosine
  • phenylphosphate
  • Macrophage Colony-Stimulating Factor
  • Receptor Protein-Tyrosine Kinases
  • Vascular Endothelial Growth Factor Receptor-1
  • Phosphoric Monoester Hydrolases
  • Inositol Polyphosphate 5-Phosphatases
  • INPPL1 protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases

Associated data

  • GENBANK/L36818
  • GENBANK/P32019
  • GENBANK/Q01968
  • GENBANK/U51742