Pleiotrophin: a cytokine with diverse functions and a novel signaling pathway.
Pleiotrophin (PTN the protein, Ptn the gene) is a 136 amino acid secreted heparin-binding cytokine that signals diverse functions, including lineage-specific differentiation of glial progenitor cells, neurite outgrowth, and angiogenesis. Pleiotrophin gene expression is found in cells in early differentiation during different development periods and upregulated in cells with an early differentiation phenotype in wound repair. The Ptn gene is a protooncogene. It is strongly expressed in different human tumor cells and expression of the Ptn gene in tumor cells in vivo accelerates growth and stimulates tumor angiogenesis. Separate independent domains have been identified in PTN to signal transformation and tumor angiogenesis. Pleiotrophin is the first ligand of any of the known transmembrane tyrosine phosphatases. Pleiotrophin inactivates the receptor protein tyrosine phosphatase (RPTP) beta/zeta. The interaction of PTN and RPTP beta/zeta increases steady-state tyrosine phosphorylation of beta-catenin. Pleiotrophin thus regulates both normal cell functions and different pathological conditions at many levels. It signals these functions through a transmembrane tyrosine phosphatase.
Deuel
Thomas F
TF
Division of Growth Regulation, Harvard Medical School, Boston, Massachusetts 02215, USA. tduel@caregroup.harvard.edu
Zhang
Nan
N
Yeh
Hsui-Jen
HJ
Silos-Santiago
Inmaculada
I
Wang
Zhao-Yi
ZY
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D002352:Carrier Proteins; D016207:Cytokines; D011518:Proto-Oncogene Proteins; C066845:pleiotrophin