HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal.

A neuronal antigen (HuD) recognized by the sera of patients with antibody-associated paraneoplastic encephalomyelitis has been isolated by screening a lambda cerebellar expression library. The recombinant antigen provides an unambiguous assay for this rare condition associated with small cell lung cancer. The recombinant antigen has been used to identify specific infiltrating lymphocytes in tumors and affected brain tissues of patients with antibody-associated paraneoplastic encephalomyelitis and sensory neuronopathy. HuD mRNA is uniquely expressed in brain tissue. The HuD protein shows a remarkable homology to the Drosophila proteins Elav and Sex-lethal and is likely to play a role in neuron-specific RNA processing.     

Analysis of deletions of the carboxyl terminus of the epidermal growth factor receptor reveals self-phosphorylation at tyrosine 992 and enhanced in vivo tyrosine phosphorylation of cell substrates.

The human epidermal growth factor receptor (EGFR) contains a large C' terminus distal to the protein tyrosine kinase domain that is conserved among members of its extended gene family. To investigate the C' terminus, a series of mutant EGFR cDNAs encoding progressive C'-terminal deletions were prepared and expressed in null recipient B82L cells. In vivo self-phosphorylation was retained in receptors truncated to residues 1052 and 1022 which lack the three identified sites of tyrosine self-phosphorylation. Receptors truncated to residue 991 did not undergo in vivo self-phosphorylation. Purified 1022 truncated receptor was self-phosphorylated to the extent of 1 mol of phosphate/mol of receptor protein. The deduced additional site of tyrosine self-phosphorylation at residue 992 was confirmed by tryptic phosphopeptide mapping and protein sequencing. EGFRs deleted to give C'-terminal residues 1052, 1022, 991, and 973 exhibited enhanced EGF-stimulated tyrosine phosphorylation of cell substrates in vivo, whereas deletion at residue 944 abolished all detectable EGF-stimulated protein tyrosine phosphorylation. These results indicate that ligand-induced self-phosphorylation is limited to the C' terminus of the EGFR and suggest that this region of the holoreceptor has an inhibitory function.