We have continued investigations which focus on identifying the biochemical signals and gene expression induced by lymphoid and myeloid growth factors. Interleukin 2 (IL 2), which stimulates that growth and differentiation of lymphoid cells, granulocyte colony stimulating factor (G-CSF), granulocytemacrophage CSF (GM-CSF) and interleukin 3 (IL 3), all which stimulate myeloid cell differentiation, were investigated. The studies have examined the early phosphorylation events induced at the membrane by each of the growth factors as well as the regulation of mRNA accumulation of at least sixteen genes. The biochemical studies included: 1) activation of specific kinases; 2) identification of kinase substrates and functional modification of the identified substrate; 3) modulation of the adenylate cyclase system; 4) activation of GTP-binding protein activity and; 5) synthesis of Ap4A nucleotides. In addition, we have examined the regulation of stable mRNA accumulation for specific genes in response to IL 2 and the above CSFs as well as cyclic AMP, an antigrowth signal for lymphoid and myeloid cell growth. We have also examined the effects of cyclic AMP analogues on IL 2 and CSF stimulated gene expression and protein synthesis. As a second major effort the laboratory has examined receptors common in the immune and central nervous systems. We have found the receptors for the cytokine interleukin 1 and human immunodeficiency virus (CD4) in brain to be indistinguishable from that observed in immune cells. In situ hybridization with cDNA probes recognizing IL 1 mRNA have localized IL 1 mRNA accumulation in normal brain. Northern analysis revealed that IL 1 beta mRNA is of a similar maturation size as that observed from monocytes. CD4 mRNA is, however, truncated in human brain as compared to T lymphocytes.
