The cellular phenotype conditions Btk for cell survival or apoptosis signaling

Bruton's agammaglobulinemia tyrosine kinase (Btk) was identified as the gene mutated in X-linked agammaglobulinemia. Btk is involved in B-cell receptor signaling and B cell ontogeny as the disease is characterized by a block in B-cell development. Cell proliferation and apoptosis are integral parts of B-cell development. We have demonstrated that overexpression of Btk in HeLa cells led to apoptosis, whereas in B cells, en dogenous levels of Btk protected the cells from apoptosis. We suggest a dual role for Btk in apoptosis and cell survival. We further propose that the phenotype of the cell may direct Btk for either cell survival or apoptosis. Our model is in line with the general feature of mammalian cells that have the inherent property to die unless the survival signals are triggered. The interplay between survival and apoptotic signaling is regulated by cell sur face receptors, cytoplasmic and nuclear regulatory molecules. These regu latory molecules may be simple unidirectional regulators or bidirectional regulators such as Btk. The different molecules involved in these pathways bring about an orchestrated signal depending on the phenotype of the cell, and a cell type-specific biological response is achieved that decides the fate of the cell.