Proline-rich tyrosine kinase2 (Pyk2) is a cytoplasmic tyrosine kinase related to focal adhesion kinase. Pyk2 expression has been known to be restricted to neuronal and hematopoietic cells and Pyk2 tyrosine phosphorylation and its kinase activity is important for the function of monocytes/macrophages. In NB4 acute promyelocytic leukemia cells, the expression of Pyk2 was increased in parallel with differentiation, and inhibited by PD98059, indicating Pyk2 expression is regulated through MAPK/ERK pathway. Dominant-negative kinase-deficient mutant of Pyk2 reduced the differentiation of NB4 cells in response to phorbol 12-mystate 13-acetate. Transcription factor CCAAT enhancer-binding protein (C/EBP) beta was required to induce Pyk2 expression in promoter analysis. These results suggest that Pyk2 is induced and involved in monocyte differentiation and C/EBPbeta is a critical regulator of the Pyk2 expression.