### A. Overview

Extracellular purines (adenosine, ADP, and ATP) and pyrimidines (UDP and UTP) are important signaling molecules that mediate diverse biological effects via cell-surface receptors termed purine receptors. In this review particular emphasis is placed on the discrepancy between the

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Receptors for Purines and Pyrimidines

The small (40S) subunit of eukaryotic ribosomes is believed to bind initially at the capped 5'-end of messenger RNA and then migrate, stopping at the first AUG codon in a favorable context for initiating translation. The first-AUG rule is not absolute, but there are rules for breaking the rule. Some anomalous observations that seemed to contradict the scanning mechanism now appear to be artifacts. A few genuine anomalies remain unexplained.

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The scanning model for translation: an update.

GTPases are conserved molecular switches, built according to a common structural design. Rapidly accruing knowledge of individual GTPases--crystal structures, biochemical properties, or results of molecular genetic experiments--support and generate hypotheses relating structure to function in other members of the diverse family of GTPases.

The GTPase superfamily: conserved structure and molecular mechanism

The protective effects of estrogen on the cardiovascular system

Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed.

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Flow-mediated endothelial mechanotransduction

Peptide and protein hormones such as glucagon and gonadotropins and neurotransmitters such as chatecholamines exert their action on target cells by binding to their respective receptors (R). These interactions lead to stimulation of cAMP formation by the adenylyl cyclase systems in these cells. In what follows we shall review and present key experimental evidences on functional aspects of cAMP forma- tion by adenylyl cyclases as seen both in the absence and presence of hormonal influence. We shall present current knowledge on the molecular composition and structure of hormone sensitive adenylyl cyclases. Taking structural as well as functional aspects into account we shall discuss current thoughts on how both hormonal stimulation and the ensuing desensitization to hormonal stimulation come about. Finally we shall present some speculations as to other forms of regulation, especially attenuation of cAMP formation and raise some of the most pertinent questions in signal transduction research.

Hormonal Regulation of Adenylyl Cyclase Activity

Screening of cDNA libraries constructed in phage or plasmids with oligonucleotide probes has becane one of the p referred cloning techniques with the least nwhr of false positive failures. I n this article we present o ur c urrent protocols for designing the procedure to detect cDNA inserts and isolate them. We illustrate with primary screens for G protein subunits and membrane receptors. A. Introduction. The use of oligonucleotide probes to screen cDNA libraries has become a method of choice to identify clones of interest. %is is due to the relative ease of screening and reduction in the identification of false positive clones. Figure 1 outlines the general strategy employed in an oligonucleotide screen. Based upn the amino acid sequence, the protein in question, an oligonucleotide probe, is synthesized. The oligonucleotide is then used to screen a cDNA library. Positive clones identified in the primary screen are isolated, subjected to secondary screening, plaque purification, South

SIGNAL TRANSDUCING G PROTEINS, RECEPrORS AND EFFM-"IDRS

G protein coupling ofreceptors toionic channels andother effector systems

Of all the receptor-coupled effector systems found in mammalian cells none has received more attention than the adenylate cyclase system (Lefkowitz et al., 1983; Smigel et al., 1984). Its ubiquity and the diversity of hormones and drugs which stimulate it has made it a premier model system for the study of the mechanisms whereby drugs and hormones activate their physiological effectors. Although numerous hormone receptors are coupled in a stimulatory or inhibitory fashion to the adenylate cyclase, to date only the β-adrenergic receptors, which respond to catecholamines such as adrenaline and noradrenaline, have been characterized in any significant detail. They are the only adenylate cyclase-coupled receptors which have been purified (Lefkowitz et al., 1983; Stiles et al., 1984a).

Juan Codina

Papers

Hormonal Regulation of Adenylyl Cyclase Activity

SIGNAL TRANSDUCING G PROTEINS, RECEPrORS AND EFFM-"IDRS

G protein coupling ofreceptors toionic channels andother effector systems

Purification, characterization and reconstitution of the adenylate cyclase-coupled β-adrenergic receptor