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(Hypertension. 2008;52:987.)
© 2008 American Heart Association, Inc.

Brief Reviews

Epidermal Growth Factor Receptor Signaling in the Kidney

Key Roles in Physiology and Disease

Wynand B.W.H. Melenhorst; Gemma M. Mulder; Qi Xi; Joost G.J. Hoenderop; Keita Kimura; Satoru Eguchi; Harry van Goor

From the Department of Pathology and Medical Biology (W.B.W.H.M., G.M.M., H.v.G.), University Medical Center Groningen and University of Groningen, Groningen, The Netherlands; Department of Physiology (Q.X., J.G.J.H.), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; and the Cardiovascular Research Center (K.K., S.E.), Department of Physiology, Temple University School of Medicine, Philadelphia, Pa.

Correspondence to Wynand B.W.H. Melenhorst, University Medical Center Groningen, Department of Pathology and Medical Biology, PO Box 196, 9700 AD Groningen, The Netherlands. E-mail w.b.w.h.melenhorst@path.umcg.nl

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Signaling through epidermal growth factor (EGF) receptors (ErbB receptors; EGFRs) is important for fundamental cellular functions, such as proliferation, migration, growth, and differentiation.¹ In human biology, ErbB signaling is involved in normal growth and development, as well as in the initiation and progression of disease. Based on the aberrant expression in a variety of malignant tumors, ErbB family members have been recognized as targets in anticancer therapy and are now used in the treatment of breast and colon malignancies.

Other than tumor biology, ErbB signaling is critically involved in renal electrolyte homeostasis. Moreover, ErbB family members are implicated in the development of end organ damage, as occurs in hypertension² and atherosclerosis.³ Therefore, the therapeutic potential of targeting ErbB receptors and ErbB signaling pathways may go beyond the field of oncology. In this review, we report on the physiological and disease-related aspects of renal ErbB signaling, with attention to potential benefits and downsides of systemic ErbB inhibition in the healthy and diseased kidney.

	ErbB Receptors: Upstream and Downstream Signaling

 
The ErbB receptor family belongs to subclass I of the receptor tyrosine kinase superfamily, incorporating epidermal growth factor (EGF) receptor (EGFR; HER1; ErbB1), HER2/neu (ErbB2), HER3 (ErbB3), and HER4 (ErbB4). All of the ErbB receptors have a common extracellular ligand-binding site, a single membrane-spanning region, and a cytoplasmic protein tyrosine kinase domain.¹ Upon ligand binding, ErbB receptors undergo conformational changes that induce the formation of receptor homo- or heterodimers. As a consequence, the intrinsic tyrosine kinase domain is activated, phosphorylating specific tyrosine residues within the cytoplasmic tail of . . . [Full Text of this Article]

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