K-ras is critical for modulating multiple c-kit-mediated cellular functions in wild-type and Nf1+/- mast cells

Waleed F. Khalaf, Feng Chun Yang, Shi Chen, Hilary White, Waylan Bessler, David Ingram, D. Clapp

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

p21ras (Ras) proteins and GTPase-activating proteins (GAPs) tightly modulate extracellular growth factor signals and control multiple cellular functions. The specific function of each Ras isoform (H, N, and K) in regulating distinct effector pathways, and the role of each GAP in negatively modulating the activity of each Ras isoform in myeloid cells and, particularly, mast cells is incompletely understood. In this study, we use murine models of K-ras- and Nf1-deficient mice to examine the role of K-ras in modulating mast cell functions and to identify the role of neurofibromin as a GAP for K-ras in this lineage. We find that K-ras is required for c-kit-mediated mast cell proliferation, survival, migration, and degranulation in vitro and in vivo. Furthermore, the hyperactivation of these cellular functions in Nf1 +/- mast cells is decreased in a K-ras gene dose-dependent fashion in cells containing mutations in both loci. These findings identify K-ras as a key effector in multiple mast cell functions and identify neurofibromin as a GAP for K-ras in mast cells.

Original languageEnglish
Pages (from-to)2527-2534
Number of pages8
JournalJournal of Immunology
Volume178
Issue number4
StatePublished - Feb 15 2007

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Mast Cells
GTPase-Activating Proteins
Neurofibromin 1
ras Proteins
Protein Isoforms
ras Genes
Myeloid Cells
Cell Survival
Intercellular Signaling Peptides and Proteins
Cell Proliferation
Mutation
protein K

ASJC Scopus subject areas

  • Immunology

Cite this

K-ras is critical for modulating multiple c-kit-mediated cellular functions in wild-type and Nf1+/- mast cells. / Khalaf, Waleed F.; Yang, Feng Chun; Chen, Shi; White, Hilary; Bessler, Waylan; Ingram, David; Clapp, D.

In: Journal of Immunology, Vol. 178, No. 4, 15.02.2007, p. 2527-2534.

Research output: Contribution to journalArticle

Khalaf, Waleed F. ; Yang, Feng Chun ; Chen, Shi ; White, Hilary ; Bessler, Waylan ; Ingram, David ; Clapp, D. / K-ras is critical for modulating multiple c-kit-mediated cellular functions in wild-type and Nf1+/- mast cells. In: Journal of Immunology. 2007 ; Vol. 178, No. 4. pp. 2527-2534.
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AU - Bessler, Waylan

AU - Ingram, David

AU - Clapp, D.

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