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Muscle cells have a biphasic response to the LG 4–5 region of laminin (E3)
Author(s) -
Zhou YanWen,
Jiang Daifemg,
Jarrett Harry W.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.818.2
Subject(s) - c2c12 , laminin , apoptosis , myocyte , annexin , protein kinase b , chemistry , microbiology and biotechnology , signal transduction , rac1 , phosphorylation , pi3k/akt/mtor pathway , myogenesis , biology , biochemistry , cell
Studies have shown that laminin or laminin α1‐chain LG4–5 domain (E3) bind to the dystrophin glycoprotein complex (DGC) on the exterior of muscle cells. This binding causes signaling through dystroglycan‐syntrophin‐grb2‐SOS1‐Rac1‐Pak1‐JNK that ultimately results in the phosphorylation of c‐Jun (Oak, Zhou, and Jarrett, J.Biol. Chem. 278:39287). Recently, we reported that laminin or E3 up‐regulates the proliferation of C2C12 myoblasts when a low concentration of E3 (<1 μg/ml) was added to cultured medium (Zhou, et al., Biochemistry, in press). Here, we show that higher concentrations of E3 (>1μg/ml) decrease cell number and cause apoptosis in C2C12 myoblasts. The increase of apoptotic cells was determined using FACS with FITC‐annexin V when 3μg/ml E3 was added to the culture medium while growing C2C12 myoblasts for 24hr. We also found that grb2 was recruited to the DGC at low E3 concentrations but not when toxic amounts of E3, which cause apoptosis, were used. These results show that muscle cells have a biphasic response to E3 and that this biphasic response is also seen in DGC signaling. Another signaling pathway originating at the DGC activates Akt and prevents apoptosis but does not involve grb2. These results suggest crosstalk between the grb2‐Rac1‐JNK pathway and the Akt one. (This work was supported by NIH AR051440 and by the Muscular Dystrophy Association, grant #3789).