Dominant negative effectors of heparin affin regulatory peptide (HARP) angiogenic and transforming activities.
Heparin affin regulatory peptide (HARP) is an heparin-binding growth factor, highly expressed in several primary human tumors and considered as a rate-limiting angiogenic factor in tumor growth, invasion, and metastasis. Implication of this protein in carcinogenesis is linked to its mitogenic, angiogenic, and transforming activities. Recently, we have demonstrated that the C-terminal residues 111-136 of HARP are required for its mitogenic and transforming activities (Bernard-Pierrot, I., Delbe, J., Caruelle, D., Barritault, D., Courty, J., and Milhiet, P. E. (2001) J. Biol. Chem. 276, 12228-12234). In this paper, HARP deleted of its last 26 amino acids was shown to act as a dominant negative effector for its mitogenic, angiogenic, transforming, and tumor-formation activities by heterodimerizing with the wild type protein. Similarly, the synthetic corresponding peptide P111-136 displayed in vitro inhibition of wild type HARP activities, but in this case, the inhibition was mainly explained by the competition of the peptide with HARP for the binding to the extracellular domain of the high affinity ALK receptor.
Bernard-Pierrot
Isabelle
I
Laboratoire de recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET), CNRS UPRES-A 7053, Université Paris XII, Avenue du Général de Gaulle, 94010 Créteil Cedex, France.
Delbé
Jean
J
Rouet
Vincent
V
Vigny
Marc
M
Kerros
Marie-Emmanuelle
ME
Caruelle
Danièle
D
Raulais
Daniel
D
Barritault
Denis
D
Courty
José
J
Milhiet
Pierre Emmanuel
PE
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001011:Aorta; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D016207:Cytokines / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000098:blood supply / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D016207:Cytokines; D006133:Growth Substances; D010446:Peptide Fragments; D011994:Recombinant Proteins; C066845:pleiotrophin