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PMID: 21155837 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Inhibitor and activator: dual functions for SHIP in immunity and cancer.

Annals of the New York Academy of Sciences ·Vol. 1217 ·2011-01-00 ·Pages 1-17

Kerr WG

Abstract

SHIP1 is at the nexus of intracellular signaling pathways in immune cells that mediate bone marrow (BM) graft rejection, production of inflammatory and immunosuppressive cytokines, immunoregulatory cell formation, the BM niche that supports development of the immune system, and immune cancers. This review summarizes how SHIP participates in normal immune physiology or the pathologies that result when SHIP is mutated. This review also proposes that SHIP can have either inhibitory or activating roles in cell signaling that are determined by whether signaling pathways distal to PI3K are promoted by SHIP's substrate (PI(3,4,5)P(3) ) or its product (PI(3,4)P(2) ). This review also proposes the "two PIP hypothesis" that postulates that both SHIP's product and its substrate are necessary for a cancer cell to achieve and sustain a malignant state. Finally, due to the recent discovery of small molecule antagonists and agonists for SHIP, this review discusses potential therapeutic settings where chemical modulation of SHIP might be of benefit.

MeSH Terms
Adjuvants, Immunologic/pharmacology,therapeutic use Animals Humans Immunity, Cellular/drug effects Immunosuppressive Agents/pharmacology,therapeutic use Inositol Polyphosphate 5-Phosphatases Neoplasms/drug therapy,enzymology,immunology,pathology Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phosphoric Monoester Hydrolases/antagonists & inhibitors,genetics,metabolism,physiology Signal Transduction/drug effects,immunology
Chemicals
Adjuvants, Immunologic Immunosuppressive Agents Phosphoric Monoester Hydrolases Inositol Polyphosphate 5-Phosphatases INPP5D protein, human Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Kerr William G
SUNY Upstate Medical University, Syracuse, New York, USA. kerrw@upstate.edu
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Article Info
Journal
Annals of the New York Academy of Sciences
Abbr.
Ann N Y Acad Sci
ISSN
1749-6632
DOI
10.1111/j.1749-6632.2010.05869.x
Email
kerrw@upstate.edu
Published
2011-01-00
Epub
2010-00-13
Pages
1-17
Language
English
Region
United States
NLM ID
7506858
PMCID
PMC4515353
Subset
IM
Grants
NHLBI NIH HHS · R01 HL72523 · United States
NHLBI NIH HHS · R01 HL085580-04 · United States
NHLBI NIH HHS · R01 HL072523-08 · United States
NHLBI NIH HHS · R01 HL085580 · United States
NHLBI NIH HHS · R01 HL107127 · United States
NHLBI NIH HHS · R01 HL HL085580 · United States
NHLBI NIH HHS · R01 HL072523 · United States
External Links
PubMed source DOI: 10.1111/j.1749-6632.2010.05869.x PMC Full Text View journal details
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