Phenylarsine oxide inhibits tyrosine phosphorylation of phospholipase Cγ2 in human platelets and phospholipase Cγ1 in NIH‐3T3 fibroblasts

FEBS Letters

Yanaga, Fumi²  Watson, Steve P.²  Asselin, Judith²  Schieven, Gary L.¹ 

[1] Department of Autoimmunity and Transplantation, Bristol Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA;University Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK

关键词: Collagen;    Fcγ receptor;    Phenylarsine oxide;    Platelet-derived growth factor-β;    Phospholipase Cγ;    Human platelet;    FcγRIIA;    the low-affinity IgG receptor;    Fcγ receptor IIA;    mAb;    monoclonal antibody;    PAO;    phenylarsine oxide;    PDGFβ;    platelet-derived growth factor-β;    PLC;    phosphoinositide-specific phospholipase C;    PVDF;    polyvinylidene difluoride;    SH;    src homology domain;   

DOI  :  10.1016/0014-5793(95)00670-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The sulphydryl reagent phenylarsine oxide (PAO) (1 μM) inhibited completely formation of inositol phosphates in human platelets induced by collagen or by cross-linking of the platelet low affinity Fc receptor, FcγRIIA, but did not alter the response to the G protein receptor agonist thrombin. PAO also inhibited completely tyrosine phosphorylation of PLCγ2 in collagen and FcγRIIA-stimulated cells, although tyrosine phosphorylation of other proteins including the tyrosine kinase syk was relatively unaffected. PAO (1 μM) also inhibited completely tyrosine phosphorylation of PLCγ1 induced by platelet derived growth factor (PDGF) in NIH-3T3 fibroblasts but only partially reduced phosphorylation of the PDGF receptor. These results provide further evidence that collagen and FcγRIIA cross-linking activate platelets through a pathway distinct from that used by thrombin and suggest that PAO may be a selective inhibitor of PLCγ relative to PLC β isozymes.

【 授权许可】

Unknown