The following extracellular heparin-binding proteins involved in regulation of growth and differentiation belong to a new family of growth factors:

• Pleiotrophin (PTN) [1]. Also known as heparin-binding growth-associated molecule (HB-GAM), heparin-binding growth factor 8 (HBGF-8), heparin- binding neutrophic factor) (HBNF) and osteoblast specific protein (OSF-1). This factor has neurite extension activity.
• Midkine (MK) [2], a retinoic acid-induced differentiation factor.
• Retinoic acid-induced heparin-binding protein (RI-HB) [3] from chicken. RI- has mitogenic activity and neurite extension activity for PC12 cells. RI-HB is possibly the chicken homolog of mammalian MK.
• Pleiotrophic factors α-1 and -2 and β-1 and -2 from Xenopus laevis [4], the homologs of respectively midkine and pleiotrophin.

These growth factors are highly related proteins of about 140 amino acids that contain 10 conserved cysteines probably involved in disulfide bonds (their position is schematically represented in the figure below). These proteins are also rich in basic residues and in tryptophan.

     xxxxxxxCxxxCxxxCxxxxxCxxxCxCxxxxCxxxxCxxxxxxxxxxCxxxxCxxxxxxxxxxxxx
           *************      *************

'C': conserved cysteine probably involved in a disulfide bond.
'*': position of the patterns.

We developed two signature patterns for this family of growth factors. As shown in the figure above, the patterns include the majority of the conserved cysteines.