Deficient Activity of Receptor-Cyclase Coupling Protein in Transformed Lymphoblasts of Patients with Pseudohypoparathyroidism, Type I*

Abstract

Erythrocytes of many patients with pseudohypoparathyroidism, type 1 (PHP-I), exhibit quantitatively reduced activity of the N protein, the guanine nucleotide-binding regulatory component of adenylate cyclase. This group of patients was designated PHP-Ia to distinguish them from PHP-Ib patients, in whom erythrocyte N activity is quantitatively normal. In Epstein-Barr virus-transformed lymphoblasts of 3 normal, 3 PHP-Ia, and 2 PHP-Ib subjects, N and adenylate cyclase activities, and cAMP accumulation and susceptibility to radiolabeling in the presence of [32P]NAD and cholera toxin were compared. In comparison to normal lymphoblasts, N activities were reduced by .apprx. 50% in lymphoblasts of the PHP-Ia patients, but were not reduced in lymphoblasts from the PHP-Ib patients. Toxin-catalyzed radiolabeling of the 42,000 MW subunit of the N protein was also reduced in lymphoblasts of the PHP-Ia patients. N deficiency apparently is generalized in tissues of PHP-Ia patients. Deficient lymphoblast N activity in PHP-Ia was not associated with decreases in adenylate cyclase activity or cAMP accumulation, probably because these activities involve many potential regulable cellular components in addition to the N protein.