Yasuo Kokai

Synergistic interaction of p185c-neu and the EGF receptor leads to transformation of rodent fibroblasts

The protein product of the rodent neu oncogene, p185neu, is a tyrosine kinase with structural similarity to the epidermal growth factor receptor (EGFR). Transfection and subsequent overexpression of the human p185c-erbB-2 protein transforms NIH 3T3 cells in vitro. However, NIH 3T3 cells are not transformed by overexpressed rodent p185c-neu. NIH 3T3 transfectants overexpressing EGF receptors are not transformed unless incompletely transformed. Several groups have recently demonstrated EGF-induced, EGFR-mediated phosphorylation of p185c-neu. During efforts to characterize the interaction of p185c-neu with EGFR further, we created cell lines that simultaneously overexpress both p185c-neu and EGFR and observed that these cells become transformed. These observations demonstrate that two distinct, overexpressed tyrosine kinases can act synergistically to transform NIH 3T3 cells, thus identifying a novel mechanism that can lead to transformation.

Molecular and functional properties of novel T cell subsets in C3H-gld/gld and nude mice. Implications for thymic and extrathymic maturation.

This review is primarily concerned with unusual subsets of thymus-derived lymphocytes which our laboratory has analyzed. One of the many difficulties encountered in the study of T-cell differentiation pathways is that the actual numbers of T-lineage cells at a given stage of development is limited. Several methods have been conceived to overcome these difilculties, including establishment of precursor T-cell clones, thymocyte tumors or hybridomas, and microculture systems. Our laboratory has taken advantage of the gid mutation, which has dramatic effects on lymphocyte accumulation and positioning patterns. We will briefly discuss T-cell differentiation in general and then describe our experiments concerning novel T-cell subsets in peripheral lymph nodes of C3Hgld/gld mice. Finally, we will discuss our views concerning the origins of these novel T-ceil subsets and their relation to normal thymic differentiation.

Receptor systems in tissues of the nervous system

A variety of receptor families mediate excitatory and growth-related functions in tissues of the nervous system. This review will focus on two members of distinct families that appear to be involved in fundamental aspects of growth and differentiation. We will describe several surface proteins known to exist on cells of the nervous system to illustrate common structural and developmental features. An in-depth analysis of the neu gene and its product and the reovirus receptor should aid in providing some insight into the diversity of elements likely to be involved in the development of complex multicellular organ systems exemplified by the central nervous system. In this review we will consider several multigene families and certain of their members which are predominantly associated with cells of the nervous system. Although little is known of the development of the complex mammalian nervous system, we will describe our recent studies analyzing developmental patterns of expression of the neu and reovirus receptor proteins. These receptors represent reasonably well-studied proteins and appear to be associated with growth and differentiation of neuronal elements.