Dual function of a bee venom serine protease: prophenoloxidase-activating factor in arthropods and fibrin(ogen)olytic enzyme in mammals.
Bee venom contains a variety of peptides and enzymes, including serine proteases. While the presence of serine proteases in bee venom has been demonstrated, the role of these proteins in bee venom has not been elucidated. Furthermore, there is currently no information available regarding the melanization response or the fibrin(ogen)olytic activity of bee venom serine protease, and the molecular mechanism of its action remains unknown. Here we show that bee venom serine protease (Bi-VSP) is a multifunctional enzyme. In insects, Bi-VSP acts as an arthropod prophenoloxidase (proPO)-activating factor (PPAF), thereby triggering the phenoloxidase (PO) cascade. Bi-VSP injected through the stinger induces a lethal melanization response in target insects by modulating the innate immune response. In mammals, Bi-VSP acts similarly to snake venom serine protease, which exhibits fibrin(ogen)olytic activity. Bi-VSP activates prothrombin and directly degrades fibrinogen into fibrin degradation products, defining roles for Bi-VSP as a prothrombin activator, a thrombin-like protease, and a plasmin-like protease. These findings provide a novel view of the mechanism of bee venom in which the bee venom serine protease kills target insects via a melanization strategy and exhibits fibrin(ogen)olytic activity.
Choo
Young Moo
YM
College of Natural Resources and Life Science, Dong-A University, Busan, Korea.
Lee
Kwang Sik
KS
Yoon
Hyung Joo
HJ
Kim
Bo Yeon
BY
Sohn
Mi Ri
MR
Roh
Jong Yul
JY
Je
Yeon Ho
YH
Kim
Nam Jung
NJ
Kim
Iksoo
I
Woo
Soo Dong
SD
Sohn
Hung Dae
HD
Jin
Byung Rae
BR
D000818:Animals; D001181:Arthropods / Q000201:enzymology*; D001514:Bee Venoms / Q000201:enzymology*; D004156:Catechol Oxidase / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D019476:Insect Proteins / Q000737:chemistry / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism / Q000494:pharmacology; D010858:Pigmentation; D011516:Prothrombin / Q000378:metabolism; D057057:Serine Proteases / Q000737:chemistry / Q000378:metabolism*; D012910:Snake Venoms / Q000201:enzymology
D001514:Bee Venoms; D004792:Enzyme Precursors; D019476:Insect Proteins; D008543:Melanins; D012910:Snake Venoms; D011516:Prothrombin; D005340:Fibrinogen; C038451:pro-phenoloxidase; D004156:Catechol Oxidase; D057057:Serine Proteases
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