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Am J Physiol Cell Physiol 279: C136-C146, 2000;
0363-6143/00 $5.00
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Vol. 279, Issue 1, C136-C146, July 2000

Osmotically relevant membrane signaling complex: association between HB-EGF, beta 1-integrin, and CD9 in mTAL

David Sheikh-Hamad1, Keith Youker2, Luan D. Truong3, Soren Nielsen4, and Mark L. Entman2

1 Renal Section, 2 Cardiovascular Sciences Section, 3 Renal Pathology Laboratory, Baylor College of Medicine, Houston, Texas 77030; and 4 Department of Cell Biology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus, Denmark

The integral membrane proteins cluster of differentiation-9 (CD9), beta 1-integrin, and heparin-binding epidermal growth factor-like (HB-EGF) exist in association in many cell lines and are linked to intracellular signaling mechanisms. Two of the proteins (CD9 and beta 1-integrin) are induced by hypertonicity, suggesting that their related signaling processes may be relevant to osmotic stress. The validity of this hypothesis rests upon coexpression and physical association between these molecules in nephron segments that are normally exposed to high and variable ambient osmolality. In this work, we show that CD9 and beta 1-integrin are induced in rat kidney medulla after dehydration. Immunohistochemistry and immunoprecipitation studies show that CD9, HB-EGF, and beta 1-integrin are coexpressed and physically associated in medullary thick ascending limbs (mTAL), nephron segments that are normally exposed to high and variable extracellular osmolality. Our findings are consistent with the existence of a cluster of integral membrane proteins in mTAL that may initiate or modulate osmotically relevant signaling pathways.

cluster of differentiation-9; heparin-binding epidermal growth factor; beta 1-integrin; osmotic stress; thick ascending limb; kidney


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