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Induction of neurite outgrowth by v-src mimics critical aspects of nerve growth factor-induced differentiation.

Abstract：

:PC12 cells treated with nerve growth factor (NGF) or infected with Rous sarcoma virus differentiate into sympathetic, neuronlike cells. To compare the differentiation programs induced by NGF and v-src, we have established a PC12 cell line expressing a temperature-sensitive v-src protein. The v-src-expressing PC12 cell line was shown to elaborate neuritic processes in a temperature-inducible manner, indicating that the differentiation process was dependent on the activity of the v-src protein. Further characterization of this cell line, in comparison with NGF-treated PC12 cells, indicated that the events associated with neurite outgrowth induced by these two agents shared features but could be distinguished by others. Both NGF- and v-src-induced neurite outgrowths were reversible. In addition, NGF and v-src could prime PC12 cells for NGF-induced neurite outgrowth, and representative early and late NGF-responsive genes were also induced by v-src. However, unlike NGF-induced neurite growth, v-src-induced neurite outgrowth was not blocked at high cell density. A comparison of phosphotyrosine containing-protein profiles showed that v-src and NGF each increase tyrosine phosphorylation of multiple cellular proteins. There was overlap in substrates; however, both NGF-specific and v-src-specific tyrosine phosphorylations were observed. One protein which was found to be phosphorylated in both the NGF- and v-src-induced PC12 cells was phospholipase C-gamma 1. Taken together, these results suggest that v-src's ability to function as an inducing agent may be a consequence of its ability to mimic critical aspects of the NGF differentiation program and raise the possibility that Src-like tyrosine kinases are involved in mediating some of the events triggered by NGF.

journal_name

Mol Cell Biol

journal_title

Molecular and cellular biology

authors

Thomas SM,Hayes M,D'Arcangelo G,Armstrong RC,Meyer BE,Zilberstein A,Brugge JS,Halegoua S

doi

10.1128/mcb.11.9.4739

subject

Has Abstract

pub_date

1991-09-01 00:00:00

pages

4739-50

issue

eissn

0270-7306

issn

1098-5549

journal_volume

pub_type

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Induction of neurite outgrowth by v-src mimics critical aspects of nerve growth factor-induced differentiation.