4.4 Article

The small GTPase Rap1 is a modulator of Hedgehog signaling

Journal

DEVELOPMENTAL BIOLOGY
Volume 409, Issue 1, Pages 84-94

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2015.10.020

Keywords

Hedgehog; Signal transduction; Morphogenesis; GTPase; Rap1

Funding

  1. SJCRH Comprehensive Cancer Center Developmental Funds from the National Cancer Institute [P30CA021765]
  2. National Institute of General Medical Science Grant [5R01GM101087]
  3. ALSAC of SJCRH
  4. SJCRH
  5. [NCIP30-CA021765]
  6. NATIONAL CANCER INSTITUTE [P30CA021765] Funding Source: NIH RePORTER
  7. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM101087] Funding Source: NIH RePORTER

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During development, the evolutionarily conserved Hedgehog (Hh) morphogen provides instructional cues that influence cell fate, cell affinity and tissue morphogenesis. To do so, the Hh signaling cascade must coordinate its activity with other morphogenetic signals. This can occur through engagement of or response to effectors that do not typically function as core Hh pathway components. Given the ability of small G proteins of the Ras family to impact cell survival, differentiation, growth and adhesion, we wanted to determine whether Hh and Ras signaling might intersect during development. We performed genetic modifier tests in Drosophila to examine the ability of select Ras family members to influence Hh signal output, and identified Rap1 as a positive modulator of Hh pathway activity. Our results suggest that Rapl is activated to its GTP-bound form in response to Hh ligand, and that the GTPase exchange factor C3G likely contributes to this activation. The Rapl effector Canoe (Cno) also impacts Hh signal output, suggesting that a C3G-Rap1-Cno axis intersects the Hh pathway during tissue morphogenesis. (C) 2015 Elsevier Inc. All rights reserved.

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