Treatment of Swiss mouse 3T3 cells and human epidermoid carcinoma A431 cells with protamine at 37 degrees C increased the 125I-epidermal growth factor (EGF) binding activity at 4 degrees C. The effect of protamine on the increase of 125I-EGF binding activity appeared to be time, temperature, and dose dependent. This up-modulation of 125I-EGF binding by protamine correlated with protamine enhanc...

Gastrin release from the antral gastrin-expressing cell (G cell) is regulated by bombesin and luminal factors. Yet, these same extracellular regulators do not stimulate expression of the gene. Since the gastric mucosa expresses large quantities of EGF receptor ligands such as TGFalpha, we examined whether EGF receptor ligands stimulate gastrin gene expression in gastrin-expressing cell cultures...

BACKGROUND Remnant lipoproteins (RLPs) have been shown to play a causative role during atherosclerosis. Furthermore, it is known that vascular smooth muscle cell (SMC) proliferation is crucial for the development of atherosclerosis and restenosis after percutaneous coronary intervention. We examined the direct effect of RLPs on the proliferation and signal transduction of SMCs. METHODS AND RE...

G protein-coupled receptors such as proteinase-activated receptor 1 induce phosphorylation of mitogen-activated protein kinases through multiple pathways including transactivation of receptor tyrosine kinases. In vascular smooth muscle cells, both matrix-metalloproteinase-dependent extracellular shedding of membrane-bound epidermal growth factor (EGF) receptor ligands and activation of the nonr...

EGF-R [EGF (epidermal growth factor) receptor] ligands can promote or inhibit cell growth. The biological outcome of receptor activation is dictated, at least in part, by ligand-specified patterns of endocytic trafficking. EGF-R trafficking downstream of the ligands EGF and TGF-alpha (transforming growth factor-alpha) has been investigated extensively. However, less is known about EGF-R fates i...

In response to epidermal growth factor (EGF), the EGF receptor is endocytosed and degraded. A substantial lag period exists between endocytosis and degradation, suggesting that endocytosis is more than a simple negative feedback. Phospholipase D (PLD), which has been implicated in vesicle formation in the Golgi, is activated in response to EGF and other growth factors. We report here that EGF r...

The association of EGF with its receptor in endosomes isolated from rat liver homogenates was assessed biochemically by polyethylene glycol precipitation and morphologically by electron microscope radioautography. The proportion of receptor-bound ligand in endosomes at 15 min after the injection of doses of 0.1 and 1 microgram EGF/100 g body weight was 57%. This value increased to 77% for the d...

Eps15 has been identified as a substrate of the EGF receptor tyrosine kinase. In this report, we show that activation of the EGF receptor by either EGF or TGF-alpha results in phosphorylation of Eps15. Stimulation of cells with PDGF or insulin did not lead to Eps15 phosphorylation, suggesting that phosphorylation of Eps15 is a receptor-specific process. We demonstrate that Eps15 is constitutive...

A variety of signal transduction pathways including PI turnover, MAP kinase activation, and PI 3-kinase activation have been shown to be affected by changes in cellular cholesterol content. However, no information is available regarding the locus (or loci) in the pathways that are susceptible to modulation by cholesterol. We report here that depletion of cholesterol with methyl-beta-cyclodextri...

Extension of the plasma membrane is one of the first steps in cell migration. Understanding how cells "choose" between various types of membrane protrusion enhances our knowledge of both normal and cancer cell physiology. The EGF receptor is a paradigm for understanding how transmembrane receptor tyrosine kinases regulate intracellular signaling following ligand stimulation. Evidence from the p...