Tβ₄ is a major actin-sequestering molecule in eukaryotic cells, and LKKTET was initially reported as a major actin-sequestering site on Tβ₄ (2). Several other residues on Tβ₄ also contribute to this important activity. An actin-binding site containing peptide with an additional amino acid, LKKTETQ, has several biological functions beyond actin-binding (Table 2). This peptide has been found in wound fluid (46), which suggests that it is a naturally occurring product of Tβ₄ degradation and that it may have physiological relevance in wounds and possibly in other normal and pathological conditions. Note that it also induces mast cell exocytosis, which could be important in wound healing. In addition, mast cells may provide additional repair factors (68, 69). This finding could be an important function in early wound healing, which helps to accelerate the wound cascade. It promotes angiogenesis both in vitro and ex vivo (9). Endothelial cell migration and tube formation in vitro have been demonstrated with LKKTETQ. Ex vivo, it promotes sprouting from aortic rings. Sprouting from aortic rings as well as cell adhesion are blocked by addition of soluble actin. One interpretation is that this peptide may function by binding to the actin on the cell surface (45). It is also possible that the actin binding to the peptide blocks accessibility of the cell surface receptor for the peptide. LKKTETQ promotes wound healing in normal rats and in aged mice and appears to be as active as the parent molecule when applied topically to full thickness dermal wounds (70). An unexpected finding was its ability also to promote hair growth when applied topically to rodent skin via activation of existing follicles. Thus, LKKTETQ is a major biologically active site for Tβ₄ and the activities with the exception of angiogenesis appear distinct from those of Ac-SDKP.

Table 2. Biological activities of the Tβ₄ peptide containing the actin-binding site (aa 17–23)

Gabriel Sosne, Ping Qiu, Allan L. Goldstein, Michelle Wheater. “The Actin Binding Site on Thymosin Β4 Promotes Angiogenesis.” FASEB, The Faseb Journal, 23 Feb. 2010, faseb.onlinelibrary.wiley.com/doi/abs/10.1096/fj.09-142307.