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To investigate the molecular basis for the diversity in muscarinic cholinergic function, we have isolated the genes encoding the human M1 and M2 muscarinic receptors (mAChR) as well as two previously undiscovered mAChR subtypes, designated HM3 and HM4. The amino acid sequence of each subtype reflects a structure consisting of seven, highly conserved(More)
Muscarinic acetylcholine receptors (mAChRs), like many other neurotransmitter and hormone receptors, transduce agonist signals by activating G proteins to regulate ion channel activity and the generation of second messengers via the phosphoinositide (PI) and adenylyl cyclase systems. Human mAChRs are a family of at least four gene products which have(More)
The primary event in the infection of cells by HIV is the interaction between the viral envelope glycoprotein, gp120, and its cellular receptor, CD4. A recombinant form of gp120 was found to bind to a recombinant CD4 antigen with high affinity. Two gp120-specific murine monoclonal antibodies were able to block the interaction between gp120 and CD4. The(More)
Human Ha-ras1 cDNAs encoding normal and activated p21 polypeptides have been efficiently expressed in Escherichia coli and the biochemical activities associated with each polypeptide compared. In addition to the guanine nucleotide binding activity, normal p21 displays a GTPase activity which is selectively impaired by a mutation which activates its(More)
DNA sequence analysis of the activated oncogene from the T24 human bladder carcinoma line and two alleles of its normal cellular progenitor (c-Ha-ras-1) indicates that the genes encompass at least four exons, and that only a single point mutation residing within the first exon distinguishes the coding region of both alleles of the normal gene from their(More)
Vertebrate genomes contain proto-oncogenes whose enhanced expression or alteration by mutation seems to be involved in the development of naturally occurring tumours. These activated genes, usually assayed by their ability to induce the malignant transformation of NIH 3T3 cells, are frequently related to the ras oncogene of Harvey (Ha-ras) or Kirsten(More)
Analysis of the organization and nucleotide sequence of two human loci related to the transforming gene of Kirsten murine sarcoma virus establishes one as a functional gene and the other as a processed pseudogene. The two final coding exons of the functional gene seem to have arisen by duplication. Differentially spliced mRNAs incorporating one or other of(More)
Little is known about the factors which regulate the growth and development of the mammalian brain. Although proliferation of neuronal cells ceases relatively early in development, certain types of glial cells proliferate and differentiate mainly perinatally. In the perinatal period, the ability of acetylcholine to stimulate phosphoinositide (PI) hydrolysis(More)
To investigate whether a particular receptor subtype can be coupled to multiple effector systems, recombinant M2 muscarinic receptors were expressed in cells lacking endogenous receptor. The muscarinic agonist carbachol both inhibited adenylyl cyclase and stimulated phosphoinositide hydrolysis. The stimulation of phosphoinositide hydrolysis was(More)