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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary amino acid sequences of several receptor tyrosine kinases have recently made it possible to deduce similarities in the molecular organization of these large multidomain proteins. This has allowed a classification of these receptors into three groups (see Waterfield this Issue and for review in Ref.1). Class I includes the EGF receptor and the neu proto-oncogene, Class II includes the insulin and insulin-like growth factor 1 (IGF-1) receptors, and Class III the platelet derived growth factor (PDGF) and the colony stimulating factor 1 (CSF-1) receptors. The conformation of the ligands for the Classes I and II receptors have been defined using X-ray diffraction, 2-D nuclear magnetic resonance (NMR) and knowledge based modelling procedures. It seems that the ligands are more diverse in sequence than the receptor tyrosine kinases so they cannot be classified as rigorously. However, certain features are common to all growth factors (so far defined) which form compact, globular structures and this allows a discussion of possible interactions between the ligand and receptor; but in the absence of a molecular structure for any of the receptors, we can only review biochemical evidence and deductions from predictive and modelling studies. Various models for the signal transduction process are discussed in the light of current work on receptor interactions.
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PMID:Structure-function relationships of growth factors and their receptors. 255 20

Overexpression and activation of the steroid receptor coactivator amplified in breast cancer 1 (AIB1)/steroid receptor coactivator-3 (SRC-3) have been shown to have a critical role in oncogenesis and are required for both steroid and growth factor signaling in epithelial tumors. Here, we report a new mechanism for activation of SRC coactivators. We demonstrate regulated tyrosine phosphorylation of AIB1/SRC-3 at a C-terminal tyrosine residue (Y1357) that is phosphorylated after insulin-like growth factor 1, epidermal growth factor, or estrogen treatment of breast cancer cells. Phosphorylated Y1357 is increased in HER2/neu (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2) mammary tumor epithelia and is required to modulate AIB1/SRC-3 coactivation of estrogen receptor alpha (ERalpha), progesterone receptor B, NF-kappaB, and AP-1-dependent promoters. c-Abl (v-Abl Abelson murine leukemia viral oncogene homolog 1) tyrosine kinase directly phosphorylates AIB1/SRC-3 at Y1357 and modulates the association of AIB1 with c-Abl, ERalpha, the transcriptional cofactor p300, and the methyltransferase coactivator-associated arginine methyltransferase 1, CARM1. AIB1/SRC-3-dependent transcription and phenotypic changes, such as cell growth and focus formation, can be reversed by an Abl kinase inhibitor, imatinib. Thus, the phosphorylation state of Y1357 can function as a molecular on/off switch and facilitates the cross talk between hormone, growth factor, and intracellular kinase signaling pathways in cancer.
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PMID:Tyrosine phosphorylation of the nuclear receptor coactivator AIB1/SRC-3 is enhanced by Abl kinase and is required for its activity in cancer cells. 1876 37