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Profiling of Signal Pathway Activation During In Vitro Lymphangiogenesis
Author(s) -
Leak Lee Virn,
Liotta Lance A.,
Calvert Vallerie S.,
Wulfkuhle Julia,
Petricoin Emmanuel F.
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.20.4.a714-a
Subject(s) - lymphangiogenesis , angiogenesis , mapk/erk pathway , phosphorylation , protein kinase b , microbiology and biotechnology , signal transduction , proteome , p38 mitogen activated protein kinases , biology , chemistry , cancer research , bioinformatics , genetics , cancer , metastasis
To profile and map protein phosphorylation events during lymphangiogenesis, we have employed an in vitro model of lymphangiogenesis coupled with reverse phase protein microarrays and phosphor‐specific antibodies, to determine the linkage of signal transduction events as LEC undergoes various phenotypic modulations during lymphangiogenesis. The level of activated ERK phosphorylation following VEGF‐C stimulation showed correlations between proliferation status versus tube forming. p38 showed variations between the various stages of lymphangiogenesis for phosphor‐p38 and total p38, of the MAPKk pathway. The ratios of phosporylated to total ERK and phosporylated to total p38 showed variations during the different stages of lymphangiogenesis. However, the ratios of phosporylated AKT to total AKT were constant, suggesting pro‐survival activation was also continuous throughout the duration of LEC differentiation. These results support a different mechanism for lymphangiogenesis versus angiogenesis and is in keeping with our previous results that the lymph proteome is distinct from plasma proteome. Employing this high throughput technology for the analysis of signal pathway profiling in LEC during lymphangiogenesis it will be possible to gain further insight into the molecular modification of proteins in LEC during various physiological and pathological conditions. .