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PMID: 8643691 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The 145-kDa protein induced to associate with Shc by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-phosphatase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 4 ·1996-02-20 ·Pages 1689-93

Damen JE, Liu L, Rosten P, Humphries RK, Jefferson AB, Majerus PW, Krystal G

Abstract

A 145-kDa tyrosine-phosphorylated protein that becomes associated with Shc in response to multiple cytokines has been purified from the murine hemopoietic cell line B6SUtA1. Amino acid sequence data were used to clone the cDNA encoding this protein from a B6SUtA1 library. The predicted amino acid sequence encodes a unique protein containing an N-terminal src homology 2 domain, two consensus sequences that are targets for phosphotyrosine binding domains, a proline-rich region, and two motifs highly conserved among inositol polyphosphate 5-phosphatases. Cell lysates immunoprecipitated with antiserum to this protein exhibited both phosphatidylinositol 3,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate polyphosphate 5-phosphatase activity. This novel signal transduction intermediate may serve to modulate both Ras and inositol signaling pathways. Based on its properties, we suggest the 145-kDa protein be called SHIP for SH2-containing inositol phosphatase.

MeSH Terms
Adaptor Proteins, Signal Transducing Adaptor Proteins, Vesicular Transport Amino Acid Sequence Animals Base Sequence Cell Line Cloning, Molecular Consensus Sequence DNA, Complementary/genetics Genes Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology Inositol Phosphates/metabolism Inositol Polyphosphate 5-Phosphatases Interleukin-3/pharmacology Mice Molecular Sequence Data Phosphatidylinositol Phosphates/metabolism Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phosphoric Monoester Hydrolases/chemistry,genetics,isolation & purification,metabolism Phosphotyrosine/analysis Protein Binding/drug effects Proteins/metabolism Recombinant Fusion Proteins/metabolism Recombinant Proteins/pharmacology Shc Signaling Adaptor Proteins Signal Transduction/physiology Src Homology 2 Domain-Containing, Transforming Protein 1 src Homology Domains
Chemicals
Adaptor Proteins, Signal Transducing Adaptor Proteins, Vesicular Transport DNA, Complementary Inositol Phosphates Interleukin-3 Phosphatidylinositol Phosphates Proteins Recombinant Fusion Proteins Recombinant Proteins Shc Signaling Adaptor Proteins Shc1 protein, mouse Src Homology 2 Domain-Containing, Transforming Protein 1 phosphatidylinositol 3,4,5-triphosphate inositol-1,3,4,5-tetrakisphosphate Phosphotyrosine Granulocyte-Macrophage Colony-Stimulating Factor phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase Phosphoric Monoester Hydrolases Inositol Polyphosphate 5-Phosphatases INPPL1 protein, human Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Damen J E
The Terry Fox Laboratory, British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada.
Liu L
Rosten P
Humphries R K
Jefferson A B
Majerus P W
Krystal G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.4.1689
Published
1996-02-20
Pages
1689-93
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC40003
Subset
IM
Grants
NHLBI NIH HHS · HL14147 · United States
NHLBI NIH HHS · HL16634 · United States
Databases
GENBANK
U39203
External Links
PubMed source DOI: 10.1073/pnas.93.4.1689 PMC Full Text View journal details
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