Recombinant Mouse Pleiotrophin/PTN Protein, CF

Pleiotrophin (PTN), also called heparin-binding growth-associated molecule (HB-GAM), heparin-binding neurotrophic factor (HBNF), heparin-affinity regulatory peptide (HARP), or osteoblast-specific factor (OSF-1), is an 18 kDa secreted, strongly heparin-binding, developmentally regulated cytokine (1 ‑ 3). PTN and midkine share 50% amino acid (aa) sequence identity, share some functions, and constitute a family (1 ‑ 3). The mouse PTN cDNA encodes 168 aa, including a 32 aa signal sequence and two thrombospondin type 1 (TSP1) beta sheet domains separated by a linker and flanked by lysine-rich N- and C-terminal sequences (4). The second TSP1 domain (aa 97 ‑ 129) contains the highest affinity binding site for heparin (4, 5). A 15 kDa form which lacks the C-terminus is mitogenic for glioblastoma cells, while full-length PTN is not (6). PTN is a highly conserved protein; human, mouse, rat, canine, porcine, equine and bovine PTN share 98% aa sequence identity or greater. During development, PTN is involved in development of brain, bone, and organs undergoing branching morphogenesis (3).  In the adult, it is induced by PDGF and upregulated in many cancers, hematopoietic stem cells and tissues undergoing remodeling (7 ‑ 10). Cell surface receptors for PTN include Syndecan-3 (which mediates neurite outgrowth) and the receptor tyrosine phosphatase PTPRB, also called RPTP beta/ zeta (3, 11 ‑ 13). Heparin binding is necessary for engaging these receptors (7, 8). PTN causes PTPRB dimerization and inactivates its phosphatase activity, which allows increased tyrosine phosphorylation of its substrates (12 ‑ 14). One such substrate is the WNT pathway molecule beta-catenin, allowing crosstalk of PTN with WNTs (12). PTN activation of the receptor ALK (anaplastic lymphoma kinase) is indirect through PTPRB, and mediates mitogenic, transforming and angiogenic activities of PTN (2, 5, 6, 13). Increased expression of PTN is correlated with neuronal development or stresses such as brain ischemia and Parkinson’s disease (2, 3, 7, 8). Both PTN and midkine have demonstrated bactericidal activity, but only in the absence of heparin (15).