By Bernard B. Brodie

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The best understood facet of insulin's mechanism is its primary interaction with its target cells via a surface membrane receptor (27,28).. To determine if NGF also interacts with a surface receptor on responsive neurons, two lines of experimentation were undertaken. First, the existence of such a receptor was investigated by testing the biological competence of insolubilized derivatives of NGF (NGF Sepharose) and second, the properties of the interaction of NGF with responsive cells was investigated with NGF radioactively labeled with io- 1 2 5 dine 125 ( I-NGF).

G. Larabee, J. Neurochem. 18, 2101-2118 (1971). R. Levi-Montalcini, Harvey Lectures 60, 217-259 (1966). R. Levi-Montalcini, Archives de Biologie 76, 387-417 (1965). R. U. W. Wolstenholme and M. , J. & A. , London) pp. 126-142 (1968). H. Angeletti, D . A. Bradshaw, Biochemistry 12, 90-100 (1973). H. A. A. Bradshaw, Biochemistry 12, 100115 (1973). H. A. Bradshaw, and R. Wade, Biochemistry 10, 463-469 (1971). S. Varon, J. M. Shooter, Proc. Nat. Acad. Sci. S. 57, 1782-1789 (1967). A. H. A. Bradshaw, Science 176, 482-487 (1972).

2 General mechanism for involvement of cAMP in the response of a cell to a hormone. The hormone binds to a receptor on the outside surface of the cell. By a mechanism as yet not elucidated this stimulates the enzyme adenyl cyclase facing the inside of the cell so that it begins to catalyse conversion of ATP into cAMP. The cAMP can either be hydrolysed by phosphodiesterase to form the innocuous metabolite 5'AMP (a reaction inhibited by caffeine and other methvl xanthines) or it can stimulate protein kinase.

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