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Science 21 December 1990:
Vol. 250. no. 4988, pp. 1690 - 1694
DOI: 10.1126/science.2270483
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Articles

Science, Vol 250, Issue 4988, 1690-1694
Copyright © 1990 by American Association for the Advancement of Science

articles

Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity

YS Li, PG Milner, AK Chauhan, MA Watson, RM Hoffman, CM Kodner, J Milbrandt, and TF Deuel

Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110.

A heparin binding mitogenic protein isolated from bovine uterus shares NH2-terminal amino acid sequence with a protein isolated from newborn rat brain. The cDNA's of the bovine, human, and rat genes have been isolated and encode extraordinarily conserved proteins unrelated to known growth or neurotrophic factors, although identity of nearly 50 percent has been found with the predicted sequence of a retinoic acid induced transcript in differentiating mouse embryonal carcinoma cells. Lysates of COS-7 cells transiently expressing this protein were mitogenic for NRK cells and initiated neurite outgrowth from mixed cultures of embryonic rat brain cells. RNA transcripts encoding this protein were widely distributed in tissues and were developmentally regulated. This protein, previously designated as heparin binding growth factor (HBGF)-8, is now renamed pleiotrophin (PTN) to reflect its diverse activities. PTN may be the first member of a family of developmentally regulated cytokines.


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Identification of Transcriptional Targets of HOXA5.
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Antisense Oligodeoxynucleotide Targeted to Midkine, a Heparin-binding Growth Factor, Suppresses Tumorigenicity of Mouse Rectal Carcinoma Cells.
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Midkine Is Involved in Neutrophil Infiltration into the Tubulointerstitium in Ischemic Renal Injury.
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Isolation of Transformation Suppressor Genes by cDNA Subtraction: Lumican Suppresses Transformation Induced by v-src and v-K-ras.
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The Chondroitin Sulfate Proteoglycans Neurocan and Phosphacan Are Expressed by Reactive Astrocytes in the Chronic CNS Glial Scar.
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A dominant-negative pleiotrophin mutant introduced by homologous recombination leads to germ-cell apoptosis in male mice.
N. Zhang, H.-J. Yeh, R. Zhong, Y.-S. Li, and T. F. Deuel (1999)
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   Abstract »    Full Text »    PDF »
Domain Structure of Pleiotrophin Required for Transformation.
N. Zhang, R. Zhong, and T. F. Deuel (1999)
J. Biol. Chem. 274, 12959-12962
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A Receptor-like Protein-tyrosine Phosphatase PTPzeta /RPTPbeta Binds a Heparin-binding Growth Factor Midkine. INVOLVEMENT OF ARGININE 78 OF MIDKINE IN THE HIGH AFFINITY BINDING TO PTPzeta.
N. Maeda, K. Ichihara-Tanaka, T. Kimura, K. Kadomatsu, T. Muramatsu, and M. Noda (1999)
J. Biol. Chem. 274, 12474-12479
   Abstract »    Full Text »    PDF »
Glycosaminoglycans Differentially Bind HARP and Modulate Its Biological Activity.
F. Vacherot, J. Delbe, M. Heroult, D. Barritault, D. G. Fernig, and J. Courty (1999)
J. Biol. Chem. 274, 7741-7747
   Abstract »    Full Text »    PDF »
Osteoblast Recruitment and Bone Formation Enhanced by Cell Matrix-associated Heparin-binding Growth-associated Molecule (HB-GAM).
S. Imai, M. Kaksonen, E. Raulo, T. Kinnunen, C. Fages, X. Meng, M. Lakso, and H. Rauvala (1998)
J. Cell Biol. 143, 1113-1128
   Abstract »    Full Text »    PDF »
Involvement of Receptor-like Protein Tyrosine Phosphatase {zeta}/RPTP{beta} and Its Ligand Pleiotrophin/Heparin-binding Growth-associated Molecule (HB-GAM) in Neuronal Migration.
N. Maeda and M. Noda (1998)
J. Cell Biol. 142, 203-216
   Abstract »    Full Text »    PDF »
Structure and Phylogenetic Analysis of an Endogenous Retrovirus Inserted into the Human Growth Factor Gene Pleiotrophin.
A. M. Schulte and A. Wellstein (1998)
J. Virol. 72, 6065-6072
   Abstract »    Full Text »    PDF »
Upregulation of Pleiotrophin Gene Expression in Developing Microvasculature, Macrophages, and Astrocytes after Acute Ischemic Brain Injury.
H.-J. Yeh, Y. Y. He, J. Xu, C. Y. Hsu, and T. F. Deuel (1998)
J. Neurosci. 18, 3699-3707
   Abstract »    Full Text »    PDF »
Cortactin-Src Kinase Signaling Pathway Is Involved in N-syndecan-dependent Neurite Outgrowth.
T. Kinnunen, M. Kaksonen, J. Saarinen, N. Kalkkinen, H. B. Peng, and H. Rauvala (1998)
J. Biol. Chem. 273, 10702-10708
   Abstract »    Full Text »    PDF »
Midkine Induces Tumor Cell Proliferation and Binds to a High Affinity Signaling Receptor Associated with JAK Tyrosine Kinases.
E. A. Ratovitski, P. T. Kotzbauer, J. Milbrandt, C. J. Lowenstein, and C. R. Burrow (1998)
J. Biol. Chem. 273, 3654-3660
   Abstract »    Full Text »    PDF »
Transformation by Ras Suppresses Expression of the Neurotrophic Growth Factor Pleiotrophin.
M. J. Corbley (1997)
J. Biol. Chem. 272, 24696-24702
   Abstract »    Full Text »    PDF »
Cellular Distribution of the Angiogenic Factor Heparin Affin Regulatory Peptide (HARP) mRNA and Protein in the Human Mammary Gland.
D. Ledoux, D. Caruelle, J.-C. Sabourin, J. Liu, M. Crepin, D. Barritault, and J. Courty (1997)
J. Histochem. Cytochem. 45, 1239-1246
   Abstract »    Full Text »    PDF »
Signal Transduction Pathways Involved in the Mitogenic Activity of Pleiotrophin. IMPLICATION OF MITOGEN-ACTIVATED PROTEIN KINASE AND PHOSPHOINOSITIDE 3-KINASE PATHWAYS.
B. Souttou, S. Ahmad, A. T. Riegel, and A. Wellstein (1997)
J. Biol. Chem. 272, 19588-19593
   Abstract »    Full Text »    PDF »
Human Breast Cancer Growth Inhibited in Vivo by a Dominant Negative Pleiotrophin Mutant.
N. Zhang, R. Zhong, Z.-Y. Wang, and T. F. Deuel (1997)
J. Biol. Chem. 272, 16733-16736
   Abstract »    Full Text »    PDF »
Dimerization of Midkine by Tissue Transglutaminase and Its Functional Implication.
S. Kojima, T. Inui, H. Muramatsu, Y. Suzuki, K. Kadomatsu, M. Yoshizawa, S. Hirose, T. Kimura, S. Sakakibara, and T. Muramatsu (1997)
J. Biol. Chem. 272, 9410-9416
   Abstract »    Full Text »    PDF »
Melanoma angiogenesis and metastasis modulated by ribozyme targeting of the secreted growth factor pleiotrophin.
F. Czubayko, A. M. Schulte, G. J. Berchem, and A. Wellstein (1996)
PNAS 93, 14753-14758
   Abstract »    Full Text »    PDF »
Human trophoblast and choriocarcinoma expression of the growth factor pleiotrophin attributable to germ-line insertion of an endogenous retrovirus.
A. M. Schulte, S. Lai, A. Kurtz, F. Czubayko, A. T. Riegel, and A. Wellstein (1996)
PNAS 93, 14759-14764
   Abstract »    Full Text »    PDF »
6B4 Proteoglycan/Phosphacan, an Extracellular Variant of Receptor-like Protein-tyrosine Phosphatase zeta /RPTPbeta , Binds Pleiotrophin/Heparin-binding Growth-associated Molecule (HB-GAM).
N. Maeda, T. Nishiwaki, T. Shintani, H. Hamanaka, and M. Noda (1996)
J. Biol. Chem. 271, 21446-21452
   Abstract »    Full Text »    PDF »
Human Ryudocan from Endothelium-like Cells Binds Basic Fibroblast Growth Factor, Midkine, and Tissue Factor Pathway Inhibitor.
T. Kojima, A. Katsumi, T. Yamazaki, T. Muramatsu, T. Nagasaka, K. Ohsumi, and H. Saito (1996)
J. Biol. Chem. 271, 5914-5920
   Abstract »    Full Text »    PDF »
Neurite Outgrowth in Brain Neurons Induced by Heparin-binding Growth-associated Molecule (HB-GAM) Depends on the Specific Interaction of HB-GAM with Heparan Sulfate at the Cell Surface.
T. Kinnunen, E. Raulo, R. Nolo, M. Maccarana, U. Lindahl, and H. Rauvala (1996)
J. Biol. Chem. 271, 2243-2248
   Abstract »    Full Text »    PDF »
Midkine Enhances Fibrinolytic Activity of Bovine Endothelial Cells.
S. Kojima, H. Muramatsu, H. Amanuma, and T. Muramatsu (1995)
J. Biol. Chem. 270, 9590-9596
   Abstract »    Full Text »    PDF »
Expression of the heparin-binding cytokines, midkine (MK) and HB-GAM (pleiotrophin) is associated with epithelial-mesenchymal interactions during fetal development and organogenesis.
T. Mitsiadis, M Salmivirta, T Muramatsu, H Muramatsu, H Rauvala, E Lehtonen, M Jalkanen, and I Thesleff (1995)
Development 121, 37-51
   Abstract »    PDF »
Regulation of development and differentiation by the extracellular matrix.
J. Adams and F. Watt (1993)
Development 117, 1183-1198
   PDF »
MK: a pluripotential embryonic stem-cell-derived neuroregulatory factor.
V. Nurcombe, N. Fraser, E. Herlaar, and J. K. Heath (1992)
Development 116, 1175-1183
   Abstract »    PDF »
Extracellular Matrix/Growth Factor Interactions.
E. Ruoslahti, Y. Yamaguchi, A. Hildebrand, and W.A. Border (1992)
Cold Spring Harb Symp Quant Biol 57, 309-315
   Abstract »    PDF »
Neuronal Cell Adhesion, Mediated by the Heparin-binding Neuroregulatory Factor Midkine, Is Specifically Inhibited by Chondroitin Sulfate E. STRUCTURAL AND FUNCTIONAL IMPLICATIONS OF THE OVER-SULFATED CHONDROITIN SULFATE.
C. Ueoka, N. Kaneda, I. Okazaki, S. Nadanaka, T. Muramatsu, and K. Sugahara (2000)
J. Biol. Chem. 275, 37407-37413
   Abstract »    Full Text »    PDF »
Haptotactic Migration Induced by Midkine. INVOLVEMENT OF PROTEIN-TYROSINE PHOSPHATASE zeta , MITOGEN-ACTIVATED PROTEIN KINASE, AND PHOSPHATIDYLINOSITOL 3-KINASE.
M. Qi, S. Ikematsu, N. Maeda, K. Ichihara-Tanaka, S. Sakuma, M. Noda, T. Muramatsu, and K. Kadomatsu (2001)
J. Biol. Chem. 276, 15868-15875
   Abstract »    Full Text »    PDF »
Identification of Anaplastic Lymphoma Kinase as a Receptor for the Growth Factor Pleiotrophin.
G. E. Stoica, A. Kuo, A. Aigner, I. Sunitha, B. Souttou, C. Malerczyk, D. J. Caughey, D. Wen, A. Karavanov, A. T. Riegel, et al. (2001)
J. Biol. Chem. 276, 16772-16779
   Abstract »    Full Text »    PDF »
The Lysine-rich C-terminal Tail of Heparin Affin Regulatory Peptide Is Required for Mitogenic and Tumor Formation Activities.
I. Bernard-Pierrot, J. Delbe, D. Caruelle, D. Barritault, J. Courty, and P. E. Milhiet (2001)
J. Biol. Chem. 276, 12228-12234
   Abstract »    Full Text »    PDF »
Pleiotrophin signals increased tyrosine phosphorylation of beta -catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta /zeta.
K. Meng, A. Rodriguez-Pena, T. Dimitrov, W. Chen, M. Yamin, M. Noda, and T. F. Deuel (2000)
PNAS 97, 2603-2608
   Abstract »    Full Text »    PDF »


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