Cripto enhances the tyrosine phosphorylation of Shc and activates mitogen-activated protein kinase (MAPK) in mammary epithelial cells.
Cripto-1 (CR-1), a recently discovered protein of the epidermal growth factor (EGF) family, was found to interact with a high affinity, saturable binding site(s) on HC-11 mouse mammary epithelial cells and on several different human breast cancer cell lines. This receptor exhibits specificity for CR-1, since other EGF-related peptides including ... EGF, transforming growth factor alpha, heparin-binding EGF-like growth factor, amphiregulin, epiregulin, betacellulin, or heregulin beta1 that bind to either the EGF receptor or to other type 1 receptor tyrosine kinases such as erb B-3 or erb B-4 fail to compete for binding. Conversely, CR-1 was found not to directly bind to or to activate the tyrosine kinases associated with the EGFR, erb B-2, erb B-3, or erb B-4 either alone or in various pairwise combinations which have been ectopically expressed in Ba/F3 mouse pro-B lymphocyte cells. However, exogenous CR-1 could induce an increase in the tyrosine phosphorylation of 185- and 120-kDa proteins and a rapid (within 3-5 min) increase in the tyrosine phosphorylation of the SH2-containing adaptor proteins p66, p52, and p46 Shc in mouse mammary HC-11 epithelial cells and in human MDA-MB-453 and SKBr-3 breast cancer cells. CR-1 was also found to promote an increase in the association of the adaptor Grb2-guanine nucleotide exchange factor-mouse son of sevenless (mSOS) signaling complex with tyrosine-phosphorylated Shc in HC-11 cells. Finally, CR-1 was able to increase p42(erk-2) mitogen-activated protein kinase (MAPK) activity in HC-11 cells within 5-10 min of treatment. These data demonstrate that CR-1 can function through a receptor which activates intracellular components in the ras/raf/MEK/MAPK pathway.
Mesh Terms:
Animals, Binding, Competitive, Breast Neoplasms, Calcium-Calmodulin-Dependent Protein Kinases, Enzyme Activation, Epidermal Growth Factor, Epithelium, Female, GPI-Linked Proteins, Growth Substances, Humans, Intercellular Signaling Peptides and Proteins, Mammary Glands, Animal, Membrane Glycoproteins, Mice, Mitogen-Activated Protein Kinase 1, Neoplasm Proteins, Phosphorylation, Protein-Tyrosine Kinases, Tumor Cells, Cultured, Tyrosine, src Homology Domains
Animals, Binding, Competitive, Breast Neoplasms, Calcium-Calmodulin-Dependent Protein Kinases, Enzyme Activation, Epidermal Growth Factor, Epithelium, Female, GPI-Linked Proteins, Growth Substances, Humans, Intercellular Signaling Peptides and Proteins, Mammary Glands, Animal, Membrane Glycoproteins, Mice, Mitogen-Activated Protein Kinase 1, Neoplasm Proteins, Phosphorylation, Protein-Tyrosine Kinases, Tumor Cells, Cultured, Tyrosine, src Homology Domains
J. Biol. Chem.
Date: Feb. 07, 1997
PubMed ID: 9013573
View in: Pubmed Google Scholar
Download Curated Data For This Publication
215911
Switch View:
- Interactions 2