Src, ras, and rac mediate the migratory response elicited by NGF and PMA in PC12 cells.

Abstract:

:The combination of nerve growth factor (NGF) and phorbol 12-myristate 13-acetate (PMA) rapidly induced the locomotion of PC12 cells by sequentially stimulating lamellar spreading, ruffling with pinocytosis, and polarization by retraction from the substratum. During migration, cells acquired long processes as a result of several undisrupted cell-substratum attachment points. The effect of NGF on PC12 migration was blocked by K-252a, a selective inhibitor of the trk family of receptor tyrosine kinases. When PMA was added to cells expressing pp60v-src, the cells displayed the same morphological behavior as they did with NGF and PMA addition. Activated ras only partially substituted for the effects of NGF; but, when ras was inhibited, the number of migrating cells decreased significantly due to a defect in spreading and retraction. Expression of an activated form of rac stimulated spontaneous growth of lamellipodia and enhanced cell migration in response to PMA. Expression of a dominant negative form of rac inhibited cell spreading and motility. Also, as a later effect, rac-inhibited cells extended much shorter neurites than wild type cells in response to NGF alone. These results indicate that the cytoarchitectural changes induced by NGF and PMA in PC12 cells are mediated by src, ras, and rac. Whereas ras and rac activation affect lamellipodia extension and retraction but not pinocytotic ruffling, src activation is involved in all three events.

journal_name

J Neurosci Res

authors

Altun-Gultekin ZF,Wagner JA

doi

10.1002/(SICI)1097-4547(19960515)44:4<308::AID-JNR

subject

Has Abstract

pub_date

1996-05-15 00:00:00

pages

308-27

issue

4

eissn

0360-4012

issn

1097-4547

pii

10.1002/(SICI)1097-4547(19960515)44:4<308::AID-JNR

journal_volume

44

pub_type

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