T and B lymphocytes express receptors for antigen on their cell surface. These receptors perform a sensory function, recognizing and binding non-self antigens complexed with proteins encoded within the major histocompatability complex (MHC). When these receptors are stimulated they relay this information to the interior of the lymphocyte through a complex series of events known as signal transduction. Signal transduction can take many forms and these forms, or pathways, are shared by many different cell types. One mechanism that lymphocytes use to relay information from the receptor to the nucleus is through enzymes known as kinases and phosphatases. Another mechanism involves the flux of ions across the cell membrane. The information relayed by these different pathways results in a specific response by the lymphocyte to its environment. These responses include proliferation, the inability to respond (anergy), or even programmed cell death. Defects or inadequacies in the molecular machinery involved in transmission of signals from the lymphocyte membrane to the nucleus are linked to cellular transformation and the inability of the immune system to respond appropriately. The emphasis of our laboratory is to understand the mechanisms by which signals that arise at the cellular membrane are relayed to the interior of the cell. Our research also focuses on the interactions between signaling pathways. To accomplish these objectives we are currently using protein chemistry, molecular biology, and tissue culture. Understanding and identifying the specific events that occur during signal transduction will aid our understanding of how these pathways are integrated, regulated, and function. This will help in the identification or treatment of different pathologies resulting from alterations in these pathways.

Chang F, Steelman LS, Lee JT, Shelton JG, Navolanic PM, Blalock WL, Franklin RA, McCubrey JA. Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 2003; 17:1263-1293.

Shelton JG, Steelman LS, Lee JT, Knapp SL, Blalock WL, Moye PW, Franklin RA, Pohnert SC, Mirza AM, McMahon M, McCubrey JA. Effects of the RAF/MEK/ERK and PI3K/AKT signal tranduction pathways on the abrogation of cytokine-dependence and prevention of apoptosis in hematopoietic cells. Oncogene 2003; 22:2478-2492.

Franklin RA. The Use of the Yeast Two-Hybrid System to Measure Protein-Protein Interactions that Occur Following Oxidative Stress. Methods Mol Biol. 2003; 218:47-57.

Chang F., Lee JT, Navolanic PM, Steelman LS, Shelton JG, Blalock WL, Franklin RA, McCubrey JA. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: A target for cancer chemotherapy. Leukemia 2003; 17:590-603.

Howe CJ, LaHair M, Maxwell JA, Lee JT, Robinson PJ, McCubrey JA, Franklin RA. Participation of the CaM-kinases in Hydrogen Peroxide-Induced I-kB Phosphorylation in Human T Lymphocytes. Journal of Biological Chemistry 2002; 277:30469-30476.

Franklin RA, Atherfold PA, Robinson PJ, Bonner D. Regulation of Pyk2 Expression by p56Lck in Jurkat T-lymphocytes. Cell. Signalling 2001; 13:65-69.

Franklin RA, Atherfold P, McCubrey JA. Calcium-induced ERK activation in human T lymphocytes occurs via p56Lck and CaM-kinase. Mol. Immunol. 2000; 37:675-683.

Franklin RA, McCubrey JA. Kinases: Positive and Negative Regulators of Apoptosis. Leukemia 2000; 14:2019-2034.

Martin EA, Robinson PJ, Franklin RA. Regulation of p16/CDK4 interactions by Oxidative Stress. Biochem. Biophys. Res. Commun. 2000; 275:764-767.