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Small GTPase Ras and Rho Expression in Rat Osteoblasts during Spaceflight
Author(s) -
KUMEI YASUHIRO,
SHIMOKAWA HITOYATA,
OHYA KEI'ICHI,
KATANO HISAKO,
AKIYAMA HIDEO,
HIRANO MASAHIKO,
MORITA SADAO
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1397.032
Subject(s) - microbiology and biotechnology , mapk/erk pathway , gtpase , signal transduction , guanine nucleotide exchange factor , small gtpase , kinase , phosphorylation , gtpase activating protein , protein kinase a , tyrosine phosphorylation , focal adhesion , biology , chemistry , g protein
: Rat osteoblasts were cultured for 4 and 5 days aboard a space shuttle and solubilized after a 24‐h treatment with 1α,25 dihydroxyvitamin D 3 . The quantitative RT‐PCR determined the mRNA levels of signaling molecules upstream and downstream Ras. The small GTPase is activated by guanine nucleotide exchange protein (GEF) and deactivated by GTPase‐activating protein (GAP). When external stimuli are transduced into intracellular signals, various pathways are recruited: focal adhesion kinase (FAK) is associated with integrin‐β, and directs tyrosine phosphorylation of downstream substrates, including phospholipase C‐γ (PLC‐γ) and son of sevenless (SOS, a Ras GEF). The mRNA levels of FAK and PLC‐γ1 and ‐γ2 in the flight cultures were increased 150% and 250% of the ground controls. The SOS mRNA levels in the flight cultures were increased 520% and 320% of the ground controls. Signals via G protein–coupled receptors are transmitted through PLC‐β and Ras GRF (another Ras GEF). Activated Ras then stimulates Raf, mitogen‐activated protein kinase (MAPK) cascades. The mRNA levels of Raf, extracellular signal‐regulated protein kinase of MAPK family (ERK‐1 and ‐2), and PLC‐β were increased during spaceflight. Rho GAP expression in the flight cultures was increased twofold of the ground controls. Since Rho GAP deactivates Rho, microgravity may suppress Rho signals, regulating actin filament rearrangement. Microgravity signals may involve two pathways (G protein–coupled receptor‐mediated pathway and tyrosine phosphorylation‐mediated pathway) that activate Ras, Raf, and MAPK cascades in rat osteoblasts.