Platelet-derived growth factor and fibronectin-stimulated migration are differentially regulated by the Rac and extracellular signal-regulated kinase pathways

Bela Anand-Apte, Bruce R. Zetter, Akila Viswanathan, Rong Guo Qiu, Jing Chen, Rosamaria Ruggieri, Marc Symons

Research output: Contribution to journalArticlepeer-review

Abstract

Directed cell migration is essential for a variety of important biological processes ranging from development and angiogenesis to metastasis. Has plays a pivotal role in the signaling cascade that governs chemotaxis of fibroblasts toward platelet-derived growth factor-BB (PDGF-BB). Ras activates multiple downstream pathways, which include the extracellular signal- regulated kinase (ERK), Rac, and Ral signaling cascades. We therefore investigated the role of the Rac and ERK pathways in cell migration. We showed that migration of fibroblasts toward PDGF-BB is inhibited by expression of dominant negative Asn-17 Rac1. Blocking of the ERK pathway by either expression of dominant negative Ala-218/Ala-222-mitogen-activated protein kinase kinase (A218/A222.MEK1) or by a MEK-specific inhibitor did not inhibit migration toward PDGF-BB. In contrast, migration toward soluble fibronectin was suppressed by inhibition of the ERK pathway but not by Ash- 17 Rac1 expression. These results indicate that directed cell migration mediated by different receptor classes in response to different ligands differentially utilizes the Rac and ERK pathways and suggest that Rac might play a critical role in pathological processes such as angiogenesis and metastasis.

Original languageEnglish (US)
Pages (from-to)30688-30692
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number49
DOIs
StatePublished - Dec 5 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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