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Proposed mechanism of heparanase-mediated activation of ERK. Step 1, elevation of heparanase (HPSE) expression in multiple myeloma cells triggers the phosphorylation/kinase activity of IR and PKC activity. Step 2, elevated PKC activity up-regulates IRS-1 expression. Step 3, high levels of IRS-1 and high IR tyrosine kinase activity up-regulates the phosphorylated levels of IRS-1. Step 4, high levels of phospho-IRS-1 up-regulate ERK activation.
