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Biomedical subjects

L Birnbaumer

Publications and source records attributed to L Birnbaumer.

304 records · Page 17Linked to original sources
PubMed1971

The reaction of glucagon with its receptor: evidence for discrete regions of activity and binding in the glucagon molecule.

Des-histidine-glucagon (DH-glucagon, glucagon(2-29)) does not activate the glucagon-sensitive adenylate cyclase system present in either liver plasma membranes or in fat-cell "ghosts", but inhibits the response of these systems to submaximal concentrations of glucagon. DH-glucagon also inhibits, competitively, the binding of [(125)I]glucagon to its receptor in liver plasma membranes. Amino-terminal fragments of glucagon (glucagon(1-21), glucagon(1-23)) and carboxy-terminal fragments (glucagon(20-29), glucagon(22-29)) failed to activate adenylate cyclase, to inhibit the response of the enzyme to glucagon, or to compete with labeled glucagon at its receptor. It is concluded that the amino-terminal histidine residue of glucagon is essential for biological activity and that a hydrophobic near-carboxy-terminal region (residues 22-27) is essential for binding of glucagon to its receptor. Amino-terminal histidine may also contribute to the binding of glucagon, since the apparent affinity of DH-glucagon for the receptor is only about one-sixth that of glucagon. Thus, essentially the entire molecule of glucagon must be considered to be the biologically active species.Because, as shown elsewhere, the binding of glucagon to its receptor shows characteristics of hydrophobic bonding, and because certain detergents induce conformational changes in the carboxy-terminal binding region of glucagon, the binding is probably of a lipophilic type.

Adenylyl Cyclases↗
PubMed1969

Glucagon-sensitive adenyl cylase in plasma membrane of hepatic parenchymal cells.

The plasma membrane of hepatic parenchymal cells contains an adenyl cyclase system that is stimulated by glucagon. Adrenocorticotropin and epinephrine do not stimulate this adenyl cyclase, and very little cyclic phospho-diesterase activity is present in the membrane. These findings support the concept that glucagon exerts its regulatory action in the liver by stimulating adenyl cyclase activity in the plasma membrane.

Adenine Nucleotides↗
PubMedDate not supplied

A role for Ni in the hormonal stimulation of adenylate cyclase.

The best understood system for transduction of extracellular messages into intracellular signals is the hormone receptor-coupled adenylate cyclase. In such systems receptors are functionally coupled to the enzyme by two special proteins, termed the stimulatory and inhibitory guanine nucleotide regulatory proteins (Ns and Ni, respectively). These proteins, thought to mediate, respectively, stimulatory and inhibitory influences on the adenylate cyclase, are members of a larger class of heterotrimeric guanine nucleotide regulatory proteins involved in membrane signal transduction. We have studied the interactions of the various components of the adenylate cyclase system by co-reconstituting pure beta-adrenergic receptors, pure Ns and Ni, and functionally resolved preparations of the catalyst in phospholipid vesicles. In the absence of Ni, beta-adrenergic receptor/Ns-mediated catecholamine stimulation of the enzyme is relatively modest (approximately 1.3-fold). Surprisingly, however, when Ni is also present, stimulation increases dramatically (up to 7-8-fold) because of a greater suppression of basal relative to agonist-stimulated enzyme activity. Thus, Ni may actually be required for maximal agonist stimulation as well as for inhibition of the adenylate cyclase.

Adenylyl Cyclases↗
PubMedDate not supplied

Signal transduction by G proteins: 1994 edition.

Findings from the last two years in signal transduction research, including the elucidation of the crystal structure of alpha1, the uncovering of multiple roles for lipidation, the mimicry of receptor action with peptides, and both the in vitro reconstitution of inhibition of adenylyl cyclase and the in cell reconstitution of receptor-G protein coupling in transient and stable expression studies, are integrated into a "current" view of the receptor --> G protein --> effector pathway. The question is raised whether receptor or betagamma is the nucleotide exchange factor, and the central participation of Mg2+ in G protein activation and the change in affinity of the G protein for Mg2+ during receptor-stimulated activation are stressed.

Adenylyl Cyclases↗