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Physiol. Rev. 79: 1283-1316, 1999;
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Physiological Reviews, Vol. 79, No. 4, October 1999, pp. 1283-1316
Copyright ©1999 by the American Physiological Society

Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor

Carl-Henrik Heldin and Bengt Westermark

Ludwig Institute for Cancer Research, Biomedical Center, and Department of Pathology, University Hospital, Uppsala, Sweden

Heldin, Carl-Henrik and Bengt Westermark. Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor. J. Neurophysiol. 79: 1283-1316, 1999. Platelet-derived growth factor (PDGF) is a major mitogen for connective tissue cells and certain other cell types. It is a dimeric molecule consisting of disulfide-bonded, structurally similar A- and B-polypeptide chains, which combine to homo- and heterodimers. The PDGF isoforms exert their cellular effects by binding to and activating two structurally related protein tyrosine kinase receptors, denoted the alpha -receptor and the beta -receptor. Activation of PDGF receptors leads to stimulation of cell growth, but also to changes in cell shape and motility; PDGF induces reorganization of the actin filament system and stimulates chemotaxis, i.e., a directed cell movement toward a gradient of PDGF. In vivo, PDGF has important roles during the embryonic development as well as during wound healing. Moreover, overactivity of PDGF has been implicated in several pathological conditions. The sis oncogene of simian sarcoma virus (SSV) is related to the B-chain of PDGF, and SSV transformation involves autocrine stimulation by a PDGF-like molecule. Similarly, overproduction of PDGF may be involved in autocrine and paracrine growth stimulation of human tumors. Overactivity of PDGF has, in addition, been implicated in nonmalignant conditions characterized by an increased cell proliferation, such as atherosclerosis and fibrotic conditions. This review discusses structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role of PDGF in normal and diseased tissues.




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 Cardiovasc ResHome page
C.-K. Lee, H. M. Lee, H. J. Kim, H.-J. Park, K.-J. Won, H. Y. Roh, W. S. Choi, B. H. Jeon, T.-K. Park, and B. Kim
Syk contributes to PDGF-BB-mediated migration of rat aortic smooth muscle cells via MAPK pathways
Cardiovasc Res, April 1, 2007; 74(1): 159 - 168.
[Abstract] [Full Text] [PDF]

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 HypertensionHome page
K. Kusaba, H. Kai, M. Koga, N. Takayama, A. Ikeda, H. Yasukawa, Y. Seki, K. Egashira, and T. Imaizumi
Inhibition of Intrinsic Interferon-{gamma} Function Prevents Neointima Formation After Balloon Injury
Hypertension, April 1, 2007; 49(4): 909 - 915.
[Abstract] [Full Text] [PDF]

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 Arterioscler. Thromb. Vasc. Bio.Home page
Y. Zheng, M. Watanabe, T. Kuraishi, S. Hattori, C. Kai, and M. Shibuya
Chimeric VEGF-ENZ7/PlGF Specifically Binding to VEGFR-2 Accelerates Skin Wound Healing via Enhancement of Neovascularization
Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 503 - 511.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
L. S. Sleer and C. C. Taylor
Cell-Type Localization of Platelet-Derived Growth Factors and Receptors in the Postnatal Rat Ovary and Follicle
Biol Reprod, March 1, 2007; 76(3): 379 - 390.
[Abstract] [Full Text] [PDF]

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 Biol. Reprod.Home page
L. S. Sleer and C. C. Taylor
Platelet-Derived Growth Factors and Receptors in the Rat Corpus Luteum: Localization and Identification of an Effect on Luteogenesis
Biol Reprod, March 1, 2007; 76(3): 391 - 400.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
T. Yoshida, Q. Gan, Y. Shang, and G. K. Owens
Platelet-derived growth factor-BB represses smooth muscle cell marker genes via changes in binding of MKL factors and histone deacetylases to their promoters
Am J Physiol Cell Physiol, February 1, 2007; 292(2): C886 - C895.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
N. G. Dolloff, M. R. Russell, N. Loizos, and A. Fatatis
Human Bone Marrow Activates the Akt Pathway in Metastatic Prostate Cells through Transactivation of the {alpha}-Platelet-Derived Growth Factor Receptor
Cancer Res., January 15, 2007; 67(2): 555 - 562.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
J. Inzunza, A. Morani, G. Cheng, M. Warner, J. Hreinsson, J.-A. Gustafsson, and O. Hovatta
Ovarian wedge resection restores fertility in estrogen receptor beta knockout (ERbeta-/-) mice
PNAS, January 9, 2007; 104(2): 600 - 605.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
B. A. Pallante, I. Duignan, D. Okin, A. Chin, M. C. Bressan, T. Mikawa, and J. M. Edelberg
Bone Marrow Oct3/4+ Cells Differentiate Into Cardiac Myocytes via Age-Dependent Paracrine Mechanisms
Circ. Res., January 5, 2007; 100(1): e1 - e11.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
Q. Xiao, L. Zeng, Z. Zhang, Y. Hu, and Q. Xu
Stem cell-derived Sca-1+ progenitors differentiate into smooth muscle cells, which is mediated by collagen IV-integrin {alpha}1/beta1/{alpha}v and PDGF receptor pathways
Am J Physiol Cell Physiol, January 1, 2007; 292(1): C342 - C352.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
Y. Kitadai, T. Sasaki, T. Kuwai, T. Nakamura, C. D. Bucana, and I. J. Fidler
Targeting the Expression of Platelet-Derived Growth Factor Receptor by Reactive Stroma Inhibits Growth and Metastasis of Human Colon Carcinoma
Am. J. Pathol., December 1, 2006; 169(6): 2054 - 2065.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
V. S. Rajkumar, X. Shiwen, M. Bostrom, P. Leoni, J. Muddle, M. Ivarsson, B. Gerdin, C. P. Denton, G. Bou-Gharios, C. M. Black, et al.
Platelet-Derived Growth Factor-{beta} Receptor Activation Is Essential for Fibroblast and Pericyte Recruitment during Cutaneous Wound Healing
Am. J. Pathol., December 1, 2006; 169(6): 2254 - 2265.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
W. Lederle, H.-J. Stark, M. Skobe, N. E. Fusenig, and M. M. Mueller
Platelet-Derived Growth Factor-BB Controls Epithelial Tumor Phenotype by Differential Growth Factor Regulation in Stromal Cells
Am. J. Pathol., November 1, 2006; 169(5): 1767 - 1783.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. Kanda, Y. Ihara, H. Murata, Y. Urata, T. Kono, J. Yodoi, S. Seto, K. Yano, and T. Kondo
Glutaredoxin Modulates Platelet-derived Growth Factor-dependent Cell Signaling by Regulating the Redox Status of Low Molecular Weight Protein-tyrosine Phosphatase
J. Biol. Chem., September 29, 2006; 281(39): 28518 - 28528.
[Abstract] [Full Text] [PDF]

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 BloodHome page
C. Rolny, I. Nilsson, P. Magnusson, A. Armulik, L. Jakobsson, P. Wentzel, P. Lindblom, J. Norlin, C. Betsholtz, R. Heuchel, et al.
Platelet-derived growth factor receptor-beta promotes early endothelial cell differentiation
Blood, September 15, 2006; 108(6): 1877 - 1886.
[Abstract] [Full Text] [PDF]

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 BloodHome page
S. H. Bengtson, S. B. Phagoo, A. Norrby-Teglund, L. Pahlman, M. Morgelin, B. L. Zuraw, L. M. F. Leeb-Lundberg, and H. Herwald
Kinin receptor expression during Staphylococcus aureus infection
Blood, September 15, 2006; 108(6): 2055 - 2063.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
L. Li, C.-H. Heldin, and P. Heldin
Inhibition of Platelet-derived Growth Factor-BB-induced Receptor Activation and Fibroblast Migration by Hyaluronan Activation of CD44
J. Biol. Chem., September 8, 2006; 281(36): 26512 - 26519.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
M. C. Mendonca, S. Q. Doi, S. Glerum, and D. F. Sellitti
Increase of C-Type Natriuretic Peptide Expression by Serum and Platelet-Derived Growth Factor-BB in Human Aortic Smooth Muscle Cells Is Dependent on Protein Kinase C Activation
Endocrinology, September 1, 2006; 147(9): 4169 - 4178.
[Abstract] [Full Text] [PDF]

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 Mayo Clin Proc.Home page
R. H. Alvarez, H. M. Kantarjian, and J. E. Cortes
Biology of Platelet-Derived Growth Factor and Its Involvement in Disease
Mayo Clin. Proc., September 1, 2006; 81(9): 1241 - 1257.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
K. Amagasaki, H. Kaneto, C.-H. Heldin, and J. Lennartsson
c-Jun N-terminal Kinase Is Necessary for Platelet-derived Growth Factor-mediated Chemotaxis in Primary Fibroblasts
J. Biol. Chem., August 4, 2006; 281(31): 22173 - 22179.
[Abstract] [Full Text] [PDF]

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 Cardiovasc ResHome page
H. C. Nystrom, P. Lindblom, A. Wickman, I. Andersson, J. Norlin, J. Faldt, P. Lindahl, O. Skott, M. Bjarnegard, S. M. Fitzgerald, et al.
Platelet-derived growth factor B retention is essential for development of normal structure and function of conduit vessels and capillaries
Cardiovasc Res, August 1, 2006; 71(3): 557 - 565.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
N. Riggi, L. Cironi, P. Provero, M.-L. Suva, J.-C. Stehle, K. Baumer, L. Guillou, and I. Stamenkovic
Expression of the FUS-CHOP Fusion Protein in Primary Mesenchymal Progenitor Cells Gives Rise to a Model of Myxoid Liposarcoma.
Cancer Res., July 15, 2006; 66(14): 7016 - 7023.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
E. J. Michaud and B. K. Yoder
The Primary Cilium in Cell Signaling and Cancer.
Cancer Res., July 1, 2006; 66(13): 6463 - 6467.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
G. M. Rivera, S. Antoku, S. Gelkop, N. Y. Shin, S. K. Hanks, T. Pawson, and B. J. Mayer
Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B
PNAS, June 20, 2006; 103(25): 9536 - 9541.
[Abstract] [Full Text] [PDF]

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 CarcinogenesisHome page
X. Chen, J. Aravindakshan, Y. Yang, R. Tiwari-Pandey, and M.R. Sairam
Aberrant expression of PDGF ligands and receptors in the tumor prone ovary of follitropin receptor knockout (FORKO) mouse
Carcinogenesis, May 1, 2006; 27(5): 903 - 915.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
Z. Chen, F. Y. Lee, K. N. Bhalla, and J. Wu
Potent Inhibition of Platelet-Derived Growth Factor-Induced Responses in Vascular Smooth Muscle Cells by BMS-354825 (Dasatinib)
Mol. Pharmacol., May 1, 2006; 69(5): 1527 - 1533.
[Abstract] [Full Text] [PDF]

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 Mol. Pharmacol.Home page
Z. Zhang and K. E. Meier
New Assignments for Multitasking Signal Transduction Inhibitors
Mol. Pharmacol., May 1, 2006; 69(5): 1510 - 1512.
[Abstract] [Full Text] [PDF]

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 Ann. Thorac. Surg.Home page
A. Koch, E. Palchyk, N. Gassler, T. J. Dengler, A. Remppis, M. Pritsch, F.-U. Sack, S. Hagl, and P. A. Schnabel
Expression of Platelet-Derived Growth Factor and Fibroblast Growth Factor in Cryopreserved Endomyocardial Biopsies Early and Late After Heart Transplant
Ann. Thorac. Surg., April 1, 2006; 81(4): 1372 - 1378.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
J.-T. Chao, L. A. Martinez-Lemus, S. J. Kaufman, G. A. Meininger, K. S. Ramos, and E. Wilson
Modulation of {alpha}7-integrin-mediated adhesion and expression by platelet-derived growth factor in vascular smooth muscle cells
Am J Physiol Cell Physiol, April 1, 2006; 290(4): C972 - C980.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
T. Ostendorf, S. Rong, P. Boor, S. Wiedemann, U. Kunter, U. Haubold, C. R.C. van Roeyen, F. Eitner, H. Kawachi, G. Starling, et al.
Antagonism of PDGF-D by Human Antibody CR002 Prevents Renal Scarring in Experimental Glomerulonephritis
J. Am. Soc. Nephrol., April 1, 2006; 17(4): 1054 - 1062.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
D. A. Klibansky, A. Chin, I. J. Duignan, and J. M. Edelberg
Synergistic targeting with bone marrow-derived cells and PDGF improves diabetic vascular function
Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1387 - H1392.
[Abstract] [Full Text] [PDF]

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 Circ. Res.Home page
A. Liden, A. Berg, T. Nedrebo, R. K. Reed, and K. Rubin
Platelet-Derived Growth Factor BB-Mediated Normalization of Dermal Interstitial Fluid Pressure After Mast Cell Degranulation Depends on {beta}3 but Not {beta}1 Integrins
Circ. Res., March 17, 2006; 98(5): 635 - 641.
[Abstract] [Full Text] [PDF]

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 BloodHome page
M. Y. Liu, M. Eyries, C. Zhang, F. S. Santiago, and L. M. Khachigian
Inducible platelet-derived growth factor D-chain expression by angiotensin II and hydrogen peroxide involves transcriptional regulation by Ets-1 and Sp1
Blood, March 15, 2006; 107(6): 2322 - 2329.
[Abstract] [Full Text] [PDF]


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