c-Kit-Mediated Overlapping and Unique Functional and Biochemical Outcomes via Diverse Signaling Pathways

Li Hong, Veerendra Munugalavadla, Reuben Kapur

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

A critical issue in understanding receptor tyrosine kinase signaling is the individual contribution of diverse signaling pathways in regulating cellular growth, survival, and migration. We generated a functionally and biochemically inert c-Kit receptor that lacked the binding sites for seven early signaling pathways. Restoring the Src family kinase (SFK) binding sites in the mutated c-Kit receptor restored cellular survival and migration but only partially rescued proliferation and was associated with the rescue of the Ras/mitogen-activated protein kinase, Rac/JNK kinase, and phosphatidylinositol 3-kinase (PI-3 kinase)/Akt pathways. In contrast, restoring the PI-3 kinase binding site in the mutated receptor did not affect cellular proliferation but resulted in a modest correction in cell survival and migration, despite a complete rescue in the activation of the PI-3 kinase/Akt pathway. Surprisingly, restoring the binding sites for Grb2, Grb7, or phospholipase C-γ had no effect on cellular growth or survival, migration, or activation of any of the downstream signaling pathways. These results argue that SFKs play a unique role in the control of multiple cellular functions and in the activation of distinct biochemical pathways via c-Kit.

Original languageEnglish
Pages (from-to)1401-1410
Number of pages10
JournalMolecular and Cellular Biology
Volume24
Issue number3
DOIs
StatePublished - Feb 2004

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Binding Sites
Phosphatidylinositol 3-Kinase
Proto-Oncogene Proteins c-kit
MAP Kinase Kinase 4
src-Family Kinases
Receptor Protein-Tyrosine Kinases
Type C Phospholipases
Growth
Phosphatidylinositols
Mitogen-Activated Protein Kinases
Cell Movement
Cell Survival
Cell Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

c-Kit-Mediated Overlapping and Unique Functional and Biochemical Outcomes via Diverse Signaling Pathways. / Hong, Li; Munugalavadla, Veerendra; Kapur, Reuben.

In: Molecular and Cellular Biology, Vol. 24, No. 3, 02.2004, p. 1401-1410.

Research output: Contribution to journalArticle

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