title: Deletion of cytoplasmic sequences of the nerve growth factor receptor leads to loss of high affinity ligand binding.
abstract: The nerve growth factor (NGF) receptor is a glycosylated transmembrane protein present on the cell surface as both high and low affinity forms, but biological responsiveness requires interactions of NGF with the high affinity site. We have tested the effects of mutations in the intracellular domain of the receptor upon its cell surface expression and equilibrium binding of 125I-NGF. Although mutant receptors lacking the entire cytoplasmic domain are processed and expressed at the cell surface and are capable of binding to NGF, the absence of cytoplasmic sequences leads to a loss of high affinity binding and to a lack of an appropriate cross-linking pattern as assessed by N-hydroxysuccinimidyl 4-azidobenzoate photoaffinity cross-linking. These results, taken together with the highly conserved nature of these cytoplasmic sequences, implies that the interaction of the receptor with an accessory molecule is necessary to form the high affinity receptor.
authors.affiliation: Department of Medicine, Cornell University Medical College, New York, New York 10021.
authors.forename: B L
authors.initials: BL
authors.lastname: Hempstead
authors.forename: N
authors.initials: N
authors.lastname: Patil
authors.forename: B
authors.initials: B
authors.lastname: Thiel
authors.forename: M V
authors.initials: MV
authors.lastname: Chao
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor; D015183:Restriction Mapping; D014162:Transfection
chemical_list: D008024:Ligands; D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor