Ras effector switching promotes divergent cell fates in C. elegans vulval patterning.

abstract

• The C. elegans vulva is patterned by epidermal growth factor (EGF) activation of Ras to control 1 fate, and 1 fate induces antagonistic Notch-dependent 2 fate. Furthermore, a spatial EGF gradient, in addition to inducing 1 fate, directly contributes to 2 fate via an unknown pathway. We find that in addition to its canonical effector, Raf, vulval Ras utilizes an exchange factor for the Ral small GTPase (RalGEF), such that Ras-RalGEF-Ral antagonizes Ras-Raf pro-1 fate activity. Consistent with its restricted expression pattern, Ral participates in EGF pro-2 activity. Thus, we have delineated a Ras effector-switching mechanism whereby position within the morphogen gradient dictates that Ras effector usage is switched to RalGEF from Raf to promote 2 instead of 1 fate. Our observations define the utility of Ras effector switching during normal development and may provide a possible mechanistic basis for cell and cancer-type differences in effector dependency and activation.

authors

• Reiner, David

published proceedings

• Dev Cell

altmetric score

• 1.25

author list (cited authors)

• Zand, T. P., Reiner, D. J., & Der, C. J.

citation count

• 56

complete list of authors

• Zand, Tanya P||Reiner, David J||Der, Channing J

publication date

• January 2011

publisher

• Elsevier  Publisher

published in

• Developmental Cell  Journal

keywords

• Amino Acid Sequence
• Animals
• Body Patterning
• Caenorhabditis Elegans
• Caenorhabditis Elegans Proteins
• Cell Lineage
• Epidermal Growth Factor
• ErbB Receptors
• Female
• Models, Biological
• Molecular Sequence Data
• Raf Kinases
• Ral Guanine Nucleotide Exchange Factor
• Ras Proteins
• Receptors, Notch
• Sequence Alignment
• Sequence Homology, Amino Acid
• Signal Transduction
• Vulva

Digital Object Identifier (DOI)

• 10.1016/j.devcel.2010.12.004

start page

• 84

end page

• 96

volume

• 20

issue

• 1

URL

• http://dx.doi.org/10.1016/j.devcel.2010.12.004