2007
DOI: 10.1182/blood-2007-03-079699
|View full text |Cite
|
Sign up to set email alerts
|

Small-molecule agonists of SHIP1 inhibit the phosphoinositide 3-kinase pathway in hematopoietic cells

Abstract: Because phosphoinositide 3-kinase (PI3K) plays a central role in cellular activation, proliferation, and survival, pharmacologic inhibitors targeting components of the PI3K pathway are actively being developed as therapeutics for the treatment of inflammatory disorders and cancer. These targeted drugs inhibit the activity of either PI3K itself or downstream protein kinases. However, a previously unexplored, alternate strategy is to activate the negative regulatory phosphatases in this pathway. The SH2-containi… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

5
178
3
1

Year Published

2008
2008
2017
2017

Publication Types

Select...
6
1

Relationship

2
5

Authors

Journals

citations
Cited by 142 publications
(194 citation statements)
references
References 53 publications
5
178
3
1
Order By: Relevance
“…SHIP1 repressor activity in mast cells is conserved in humans, and agonists and antagonists of SHIP1 function have recently been identified and tested in vivo (40,41). Our study suggests that SHIP1 agonists could reduce the severity of anaphylaxis, allergic asthma, and other mast cell-associated diseases in humans.…”
Section: Discussionmentioning
confidence: 66%
“…SHIP1 repressor activity in mast cells is conserved in humans, and agonists and antagonists of SHIP1 function have recently been identified and tested in vivo (40,41). Our study suggests that SHIP1 agonists could reduce the severity of anaphylaxis, allergic asthma, and other mast cell-associated diseases in humans.…”
Section: Discussionmentioning
confidence: 66%
“…2). Hence, these structural domains are able to support the relocalization of SHIP from the cytosol to the plasma membrane, where its catalytic activity regulates PtdIns(3,4,5)P 3 accumulation (22,24). In addition, these structural features and binding motifs allow SHIP to serve a scaffolding role for the recruitment of other proteins to the plasma membrane independent of catalytic function.…”
Section: A Fleet Of Multitasking Ship Moleculesmentioning
confidence: 99%
“…Conversely, inhibitors of lipid phosphatases might be expected to improve T lymphocyte function either during immunodeficiency syndromes or as part of antitumor therapies. Of particular note is the recent identification of pelorol, a meroterpenoid originally isolated from the marine sponge Dactylospongia elegans as an activator of SHIP (24). More potent synthetic analogs of pelorol have been shown to exhibit anti-inflammatory effects in in vitro and in vivo models (24).…”
Section: Lipid Phosphatases As Targets For Drug Discoverymentioning
confidence: 99%
See 2 more Smart Citations