Abstract：
:Adult rat chromaffin cells may proliferate or extend neurites when stimulated by nerve growth factor (NGF) but their response is predominantly proliferative, making them a unique model for studying how mitogenic specificity is achieved. We examined contributions of the NGF receptors trk and p75 and of the major NGF signaling pathways to proliferation versus neurite outgrowth. The type of initial NGF response does not correlate with intensity of immunoreactivity for trk or p75. However, proliferation is initiated at lower NGF concentrations than neurite outgrowth, suggesting that it requires a less intense signal. Mitogenic cooperativity between receptors at low NGF concentrations is suggested by inhibitory effects of p75-blocking antibodies, but responses to trk-agonist antibody indicate that trk activation alone can induce proliferation. NGF-induced phosphorylation of ras-mediated mitogen-activated protein kinases (MAPK) Erk1 and Erk2 is as prolonged in normal chromaffin cells as in PC12 cells, where NGF is neuritogenic. Trk-agonist antibody, which is as mitogenic as NGF but less neuritogenic, causes equally prolonged but less intense ERK phosphorylation. The MAPK kinase(MEK-1) inhibitor PD98059 partially inhibits Erk phosphorylation and does not inhibit chromaffin cell proliferation, while depolarization selectively inhibits proliferation without blocking Erk phosphorylation. Proliferation is markedly reduced by the phosphoinositol-3 (PI-3) kinase inhibitor LY294002 while downregulation of protein kinase C (PKC) causes no change. These findings suggest that low-level, rather than short-duration, stimulation of NGF signaling pathways causes NGF to be mitogenic. Ras-mediated MAPK activation may be more critical in neurite outgrowth than in proliferation and PI-3 kinase may be the major mitogenic determinant.
journal_name
Cell Tissue Resjournal_title
Cell and tissue researchauthors
Powers JF,Shahsavari M,Tsokas P,Tischler ASdoi
10.1007/s004410051209subject
Has Abstractpub_date
1999-01-01 00:00:00pages
21-32issue
1eissn
0302-766Xissn
1432-0878journal_volume
295pub_type
杂志文章abstract：:The spatial and temporal distribution of three peptides, DSK I, DSK II, and DSK 0, encoded by the Drosophila melanogaster drosulfakinin (Dsk) gene, have been examined in the central nervous system. DSK I and DSK II have a -RFamide C-terminus and are structurally similar to sulfakinin peptides; in contrast, DSK 0 conta...
journal_title：Cell and tissue research
pub_type： 杂志文章
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journal_title：Cell and tissue research
pub_type： 杂志文章
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journal_title：Cell and tissue research
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journal_title：Cell and tissue research
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journal_title：Cell and tissue research
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journal_title：Cell and tissue research
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journal_title：Cell and tissue research
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journal_title：Cell and tissue research
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journal_title：Cell and tissue research
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pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Cell and tissue research
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journal_title：Cell and tissue research
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journal_title：Cell and tissue research
pub_type： 杂志文章
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