Thymosin beta4 is released from human blood platelets and attached by factor XIIIa (transglutaminase) to fibrin and collagen.
The beta-thymosins constitute a family of highly conserved and extremely water-soluble 5 kDa polypeptides. Thymosin beta4 is the most abundant member; it is expressed in most cell types and is regarded as the main intracellular G-actin sequestering peptide. There is increasing evidence for extracellular functions of thymosin beta4. For example, thymosin beta4 increases the rate of attachment and spreading of endothelial cells on matrix components and stimulates the migration of human umbilical vein endothelial cells. Here we show that thymosin beta4 can be cross-linked to proteins such as fibrin and collagen by tissue transglutaminase. Thymosin beta4 is not cross-linked to many other proteins and its cross-linking to fibrin is competed by another family member, thymosin beta10. After activation of human platelets with thrombin, thymosin beta4 is released and cross-linked to fibrin in a time- and calcium-dependent manner. We suggest that thymosin beta4 cross-linking is mediated by factor XIIIa, a transglutaminase that is coreleased from stimulated platelets. This provides a mechanism to increase the local concentration of thymosin beta4 near sites of clots and tissue damage, where it may contribute to wound healing, angiogenesis and inflammatory responses.
Huff
Thomas
T
Institute of Biochemistry, Faculty of Medicine, University Erlangen-Nuremberg, 91054 Erlangen, Germany. thymosin@biochem.uni-erlangen.de
Otto
Angela M
AM
Müller
Christian S G
CS
Meier
Markus
M
Hannappel
Ewald
E
D000199:Actins / Q000378:metabolism; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism*; D026122:Factor XIIIa / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D013947:Thymosin / Q000097:blood* / Q000378:metabolism; D000099201:Thymosin beta(4)
D000199:Actins; D002118:Calcium; D003094:Collagen; D026122:Factor XIIIa; D005337:Fibrin; D005340:Fibrinogen; D013947:Thymosin; D000099201:Thymosin beta(4); C039302:thymosin beta(10)