CHROMOSOME LOCATIONS OF GENES ENCODING HUMAN SIGNAL-TRANSDUCTION ADAPTER PROTEINS, NCK (NCK), SHC (SHC1), AND GRB2 (GRB2)

Abnormalities due to chromosomal aberration or point mutation in gene products of growth factor receptors or in ras gene products, which lie on the same signaling pathway, can cause disease in animals and human s. Thus, it can be important to determine chromosomal map positions of genes encoding ''adapter'' proteins, which are involved in transducin g signals from receptor tyrosine kinases to downstream signal recipien ts such as ras, because adaptor protein genes could also, logically, s erve as targets of mutation, rearrangement, or other aberration in dis ease. Therefore, DNAs from panels of rodent-human hybrids carrying def ined complements of human chromosomes were assayed for the presence of the cognate genes for NCK, SHC, and GRB2, three SH2 or SH2/SH3 (Src h omology 2 and 3) domain-containing adapter proteins. Additionally, NCK and SHC genes were more narrowly localized by chromosomal in situ hyb ridization. The NCK locus is at chromosome region 3q21, a region invol ved in neoplasia-associated changes; the SHC cognate locus, SRC1, is a t 1q21, and the GRB2 locus is at 17q22-qter telomeric to the HOXB and NGFR loci. Both SHC1 and GRB2 are in chromosome regions that may be du plicated in some tumor types. (C) 1994 Academic Press, Inc.