Expression of trk in MAH cells lacking the p75 low-affinity nerve growth factor receptor is sufficient to permit nerve growth factor-induced differentiation to postmitotic neurons.
We have transfected MAH cells, an immortalized sympathoadrenal progenitor cell line, with a plasmid encoding the 140-kDa Trk protein, a nerve growth factor (NGF) receptor with protein-tyrosine kinase activity. NGF promotes neurite outgrowth and proliferation from such cells, indicating that Trk is sufficient to mediate such responses in the absence of significant levels of the endogenous 75-kDa low-affinity NGF receptor (p75). These initial NGF responses are indistinguishable from those evoked by basic fibroblast growth factor (bFGF). However, NGF is sufficient to promote terminal differentiation of a approximately 8% of trk-transfected MAH cells to postmitotic, NGF-dependent neurons, whereas all cells eventually die in medium with bFGF. Other environmental signals (such as depolarization or ciliary neurotrophic factor) can cooperate with NGF to enhance production of postmitotic NGF-dependent neurons in trk-transfected MAH cells. The terminal differentiation of sympathetic neurons thus involves sequential and cooperative actions of different growth and neurotrophic factors, as well as cell-intrinsic changes in the response to these factors.
Verdi
J M
JM
Division of Biology, California Institute of Technology, Pasadena 91125.
Ip
N
N
Yancopoulos
G D
GD
Anderson
D J
DJ
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins; D014162:Transfection
D017931:DNA Primers; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA