Protein phosphorylation in K562 cells(human pre-erythrocyte leukemia) transitting from $G_0$ to S phase of cell cycle was examined. The 100 kDa and 120 kDa protein of molecular weight were specifically phosphorylated in 30 minutes after serum addition and remained phosphorylated for 4 hours. Cellular levels of second messenger molecules during the progresseion of cell cycle from G0 to S phase were monitored. Rapid increase of $IP_3$ contents were observed in 30 minutes after the addition of serum to the culture media. There were temporary elevation of calcium concentration in parallel with the increase of $IP_3$ contents. The phosphorylation of 100 kDa and 120 kDa proteins were inhibited by addition of CaM kinase inhibitor, calmidazolium. Data indicates that CaM kinase is the major kinase responsible for the phosphorylation of the 100kDa and 120 kDa proteins, which might be involved with the initiation of DNA synthesis in S phase of the cell cycle.