This proposal is part of a project whose overall aim is to identify macrophage products of potential importance for understanding and treating cancer as well as other clinical disorders. Differential, screening of a cDNA library prepared from a mouse macrophage-like cell line has led to the identification of 11 mRNA species of increased abundance following exposure to gamma-interferon. Two of these mRNA species, designated 119/MIG and CRG-2 encode previously undescribed members of a newly-defined family of small secreted proteins that includes platelet factor 4, melanoma growth stimulatory activity (MGSA/gro) and IL-8 among others. Using the 119/MIG cDNA probe a new human member of the family, MIG-2, has been discovered. The purpose of this proposal is to study the 119/MIG, CRG-2 and MIG-2 genes and proteins in order to identify their biological activities.
The specific aims are: to determine the tissues and cell types where the 119/MIG and CRG-2 proteins are made by using nucleic acid probes and antibodies; to prepare and purify the 119/MIG and CRG-2 proteins characterize the structure, and the functional properties of the 119/MIG and CRG-2 proteins using the purified proteins and antibodies; to complete the initial characterization of the MIG-2 gene and protein and use MIG-2 to extend the mouse work to human systems. 119/MIG, CRG-2 and MIG-2 are macrophage-derived, interferon-induced members of a family of secreted proteins whose members are active as regulators of cell growth and immune cell activation. These associations make 119/MIG, CRG-2, and MIG-2 of interest as potential regulators of normal and neoplastic cell growth and immune cell activation, and as mediators of the effects of the interferons, such as the activation of macrophages for tumor cell cytotoxicity.
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