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Effects of the monomeric disintegrin eristostatin on melanoma intracellular protein tyrosine phosphorylation
Author(s) -
Hensley Brett David,
PaquetteStraub Carrie,
McLane MaryAnn
Publication year - 2006
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.20.5.a925-a
Subject(s) - disintegrin , phosphorylation , tyrosine phosphorylation , chemistry , tyrosine , cell culture , microbiology and biotechnology , biology , biochemistry , metalloproteinase , matrix metalloproteinase , genetics
Disintegrins, low molecular weight proteins isolated from snake venom, can interact with many cell types and adhesion molecules. One disintegrin, eristostatin (Er), has the ability to inhibit platelet aggregation and human and murine melanoma cell metastasis. Recent studies using wound healing assays suggest that Er may inhibit melanoma cell motility. No mechanism elucidating Er's mode of inhibition has been discovered thus far. Using immunoprecipitaton with antiphosphotyrosine antibody, we evaluated the effect of Er (3000nM) on tyrosine phosphorylation of intracellular proteins within five human melanoma cell lines: C8161, M24met, 1205 LU, MV3, and WM164. We determined that Er notably changed the protein phosphorylation within all five cell lines. The 1205 LU cell line showed an increase in protein phosphorylation from 100–140 kDa, 60–75 kDa, and 37–45 kDa when treated with Er compared to cells treated with water. M24met cells showed a similar increase in protein phosphorylation at 95–100 kDa and 40–45 kDa when treated with Er. A decrease in protein phosphorylation was found at 40–45 kDa for Er‐treated C8161 cells and at 95–100 kDa and 135–140 kDa for Er‐treated MV3 cells. Er‐treated WM164 cells showed a decrease in protein phosphorylation at 55–60 kDa and 135–140 kDa as well as an increase at 125–130 kDa. A review of all known tyrosine phosphorylated proteins involved with cellular motility provided many possible candidates including Pten, EGFR, Fak, FGFR, PDGFR, Pyk2, Hck, and others. Research supported by NIH ( CAO98056 , MAM) and Charles Peter White Scholarship (BH).