Insulin-like growth factor I (IGF-I) exists in the blood at a high concentration and in various tissues. IGF-I may positively participate in the process of tumor metastasis, since it has various biological activities in addition to growth promoting activity for many cell types including malignant cells. We found a highly metastatic cell line (colon 26 NL-17) the growth of which IGF-I strongly promoted. Investigation of the mechanism of signal transduction of IGF-I in the NL-17 cells revealed two cytoplasmic proteins (pp150 and pp160) which were immediately tyrosine-phosphorylated upon IGF-I stimulation and enabled to bind to phosphatidyl inositol 3-kinase. The pp150 and pp160 may be important mediators of IGF-I signal.