Cell cycle phase-specific surface expression of nerve growth factor receptors TrkA and p75(NTR).
Expression of the nerve growth factor (NGF) receptors TrkA and p75(NTR) was found to vary at the surface of PC12 cells in a cell cycle phase-specific manner. This was evidenced by using flow cytometric and microscopic analysis of cell populations labeled with antibodies to the extracellular domains of both receptors. Differential expression of these receptors also was evidenced by biotinylation of surface proteins and Western analysis, using antibodies specific for the extracellular domains of TrkA and p75(NTR). TrkA is expressed most strongly at the cell surface in M and early G1 phases, whereas p75(NTR) is expressed mainly in late G1, S, and G2 phases. This expression reflects the molecular and cellular responses to NGF in specific phases of the cell cycle; in the G1 phase NGF elicits both the anti-mitogenic effect, i.e., inhibition of the G1 to S transition, and the differentiation response whereas a survival effect is provoked elsewhere in the cell cycle. A model is proposed relating these responses to the surface expression of the two receptors. These observations open the way for novel approaches to the investigation of the mechanism of NGF signal transduction.
Laboratoire de Biologie Moléculaire et Cellulaire, Unité Mixte de Recherche 49, Centre National de la Recherche Scientifique, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France.
J L
JL
Urdiales
E
E
Becker
M
M
Andrieu
A
A
Thomas
J
J
Jullien
L A
LA
van Grunsven
S
S
Menut
G I
GI
Evan
D
D
Martín-Zanca
B B
BB
Rudkin
D000818:Animals; D019921:Biotinylation; D002453:Cell Cycle / Q000502:physiology*; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis*; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis*
D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA