The complete 1,210-amino acid sequence of the human epidermal growth factor (EGF) receptor precursor, deduced from cDNA clones derived from placental and A431 carcinoma cells, reveals close similarity between the entire predicted v-erb-B mRNA oncogene product and the receptor transmembrane and cytoplasmic domains. A single transmembrane region of 23 amino acids separates the extracellular EGF binding and cytoplasmic domains. The receptor gene is amplified and apparently rearranged in A431 cells, generating a truncated 2.8-kilobase mRNA which encodes only the extracellular EGF binding domain.

We have deduced the entire 1,370-amino-acid sequence of the human insulin receptor precursor from a single complementary DNA clone. The precursor starts with a 27-amino-acid signal sequence, followed by the receptor alpha-subunit, a precursor processing enzyme cleavage site, then the beta-subunit containing a single 23-amino-acid transmembrane sequence. There are sequence homologies to human epidermal growth factor receptor and the members of the src family of oncogene products.

To identify structural characteristics of the closely related cell surface receptors for insulin and IGF‐I that define their distinct physiological roles, we determined the complete primary structure of the human IGF‐I receptor from cloned cDNA. The deduced sequence predicts a 1367 amino acid receptor precursor, including a 30‐residue signal peptide, which is removed during translocation of the nascent polypeptide chain. The 1337 residue, unmodified proreceptor polypeptide has a predicted Mr of 151,869, which compares with the 180,000 Mr IGF‐I receptor precursor. In analogy with the 152,784 Mr insulin receptor precursor, cleavage of the Arg‐Lys‐Arg‐Arg sequence at position 707 of the IGF‐I receptor precursor will generate alpha (80,423 Mr) and beta (70,866 Mr) subunits, which compare with approximately 135,000 Mr (alpha) and 90,000 Mr (beta) fully glycosylated subunits.

A novel potential cell surface receptor of the tyrosine kinase gene family has been identified and characterized by molecular cloning. Its primary sequence is very similar to that of the human epidermal growth factor receptor and the v-erbB oncogene product; the chromosomal location of the gene for this protein is coincident with the neu oncogene, which suggests that the two genes may be identical.

Vascular development is a complex but orderly process that is tightly regulated. A number of secreted factors produced by surrounding cells regulate endothelial cell (EC) differentiation, proliferation, migration and coalescence into cord-like structures. Vascular cords then undergo tubulogenesis to form vessels with a central lumen. But little is known about how tubulogenesis is regulated in vivo. Here we report the identification and characterization of a new EC-derived secreted factor, EGF-like domain 7 (Egfl7). Egfl7 is expressed at high levels in the vasculature associated with tissue proliferation, and is downregulated in most of the mature vessels in normal adult tissues. Loss of Egfl7 function in zebrafish embryos specifically blocks vascular tubulogenesis. We uncover a dynamic process during which gradual separation and proper spatial arrangement of the angioblasts allow subsequent assembly of vascular tubes. This process fails to take place in Egfl7 knockdown embryos, leading to the failure of vascular tube formation. Our study defines a regulator that controls a specific and important step in vasculogenesis.

Nerve growth factor (NGF) is thought to have a profound effect on the development and maintenance of sympathetic and embryonic sensory neurones (see refs 1-3 for review). NGF activity isolated from the male mouse submaxillary gland (MSG) consists of three types of subunits, alpha, beta and gamma, which specifically interact to form a 7S, approximately 130,000-molecular weight (Mr) complex. The 7S complex contains two identical 118-amino acid beta-chains, which are solely responsible for the nerve growth-stimulating activity of NGF. While NGF is found in almost all vertebrates, most research has focused on murine NGF, as the mouse male submaxillary gland contains higher levels of this polypeptide than other tissues. Even so, beta-NGF comprises only approximately 0.1% of the protein in this small gland, which has made the study of this polypeptide difficult. The amino acid sequence of the mouse NGF beta-chain has been determined and some information has been obtained regarding the size of a mouse precursor molecule, pro-beta-NGF, but little was known about the structure and relatedness of beta-NGF from other vertebrates. Here we describe the isolation of mouse beta-NGF complementary DNA (cDNA) and present its nucleotide sequence, which predicts a prepro-beta-NGF molecule of Mr 27,000 (27K) and a pro-beta-NGF molecule of Mr 25K. We have used the mouse beta-NGF cDNA clone to isolate the human beta-NGF gene, the coding regions of which are highly homologous to the mouse prepro-beta-NGF nucleotide and amino acid sequences.

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The tyrosine kinases Flt4, Fltl, and Flkl (or KDR) constitute a family of endothelial cell-specific receptors with seven immunoglobulin-like domains and a split kinase domain. Fltl and Flkl have been shown to play