The laboratory has principally been involved in the study of receptor signal transduction for two growth regulators, interleukin 2 (IL 2) and prolactin. Both """"""""cytokines"""""""" have some growth promoting activity on lymphocytes, while prolactin can also effect growth and differentiation of breast carcinoma cell lines. Much of our work has focused on the purification and identification of enzymatic proteins associated with the respective receptor complexes. The primary tyrosine kinase(s) associated with these receptors was identified as members of a recently discovered family of tyrosine protein kinases termed, JAK. JAK-2 was found to be the principal protein tyrosine kinase (PTK) associated with the prolactin receptor, whereas a newly discovered member of the JAK-family, JAK-3/L- JAK, was shown to be associated with the IL 2 receptor. We have cloned the rat form of JAK-2 and are involved in structure-function studies of this enzyme. Using receptor deletion mutants we have mapped the cytoplasmic regions of the receptors to determine the structural requirements for interaction with these PTKs. Furthermore, two other proteins found in the IL 2R complex (97 kD, 180 kD) were purified and microsequenced. The 180 kD sequence wa unique and molecular cloning is underway. We have developed a baculovirus expression system to produce quantities of mutant prolactin. The mutant prolactin molecules will be used to test for antagonistic activity on breast carcinoma cell lines. Our AIDS related studies have expanded to look at TNF receptor related receptors CD27. Treatment of HI chronically infected cells with anti-CD27 was shown to inhibit the production of HIV p24.
