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Previous Volume 340:1012-1020 April 1, 1999 Number 13 Next

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Disease-causing mutations often reveal key pathways of physiologic regulation and their underlying molecular mechanisms. Mutations in the trimeric guanine nucleotide-binding proteins (G proteins), which relay signals initiated by photons, odorants, and a host of hormones and neurotransmitters, cause many diseases. For the most part, the diseases are confined to a set of fascinating but rare endocrine disorders (Table 1).¹ A recent study suggests that mutations in G proteins can also lead to essential hypertension.² If this study is correct, hypertension may be one of several common disorders caused by defects in this ubiquitous family of signaling molecules.

View this table: [in this window] [in a new window]   Table 1. Diseases . . . [Full Text of this Article]

 
Structure and Function of G Proteins

Defects in the Termination of G Protein Signaling

Cholera

Acromegaly

Other Activating Mutations in G

Regulators of GTP Hydrolysis

Genetic Inactivation of G Protein Subunits

Pseudohypoparathyroidism Type I

Other Potential Mutations in G Proteins

Abnormal Initiation of the G Protein Signal

Pertussis

Specifically Impaired Activation of G_s in Pseudohypoparathyroidism Type Ia

Testotoxicosis with Pseudohypoparathyroidism Type Ia

Essential Hypertension

Conclusions

Source Information

From the Department of Medicine E and the Laboratory of Biochemical Pharmacology, Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel (Z.F.); the Departments of Cellular and Molecular Pharmacology and Medicine and the Cardiovascular Research Institute, University of California, San Francisco (H.R.B.); and the Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan (T.I.).

Address reprint requests to Dr. Iiri at the Fourth Department of Internal Medicine, University of Tokyo School of Medicine, 3-28-6 Mejirodai, Bunkyo-ku, Tokyo 112, Japan, or at tiiri-tky@umin.ac.jp.

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