Bm-TFF2, a trefoil factor protein with platelet activation activity from frog Bombina maxima skin secretions.
In mammals, trefoil factor family (TFF) proteins are involved in mucosal maintenance and repair, and they are also implicated in tumor suppression and cancer progression. A novel two domain TFF protein from frog Bombina maxima skin secretions (Bm-TFF2) has been purified and cloned. It activated human platelets in a dose-dependent manner and activation of integrin alpha(IIb)beta(3) was involved. Aspirin and apyrase did not largely reduce platelet response to Bm-TFF2 (a 30% inhibition), indicating that the aggregation is not substantially dependent on ADP and thromboxane A2 autocrine feedback. Elimination of external Ca(2+) with EGTA did not influence the platelet aggregation induced by Bm-TFF2, meanwhile a strong calcium signal (cytoplasmic Ca(2+) release) was detected, suggesting that activation of phospholipase C (PLC) is involved. Subsequent immunoblotting revealed that, unlike in platelets activated by stejnulxin (a glycoprotein VI agonist), PLCgamma2 was not phosphorylated in platelets activated by Bm-TFF2. FITC-labeled Bm-TFF2 bound to platelet membranes. Bm-TFF2 is the first TFF protein reported to possess human platelet activation activity.
Zhang
Jie
J
Department of Animal Toxinology, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
Zhang
Yong
Y
Wan
Shao-Gui
SG
Wei
Shuang-Shuang
SS
Lee
Wen-Hui
WH
Zhang
Yun
Y
D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D009124:Muscle Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D011485:Protein Binding; D012867:Skin / Q000378:metabolism; D000071164:Trefoil Factor-2
D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; C000604007:TFF2 protein, human; D000071164:Trefoil Factor-2; D002118:Calcium