Analysis of tyrphostin AG1478 effect on behavior of internalized EGF receptor at different stages of endocytosis

Кондратов, К. А.; Chernorudskiy, Alexander; Amosova, A. P.; Корнилова, Е. С.

doi:10.1134/s1990519x09050083

Cited by 1 publication

(2 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, it has been demonstrated that PD158780, another EGF receptor tyrosine kinase inhibitor, also affected early steps of internalization [Sorkina et al, 2002;Wolf et al, 2011]. Thus, it is possible that these inhibitors may work at different steps during endocytosis of EGF-receptor by affecting the recruitment of selective factors [Thomas et al, 2003;Kondratov et al, 2010]. PD158780 prevented the targeting of EGF-receptor into coated pits by altering the recruitment of subunits of the AP2 complex [Sorkina et al, 2002].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we raised the question of whether tyrosine kinase activity of the EGF-receptor is also required in the fusion between endosomes. To investigate this requirement, we first examined the effect of AG1478 inhibitor [Yamamoto et al, 2006;Kondratov et al, 2010] on the fusion reaction. As a control, we also examined the effect of an inactive tyrosine kinase inhibitor (AG9).…”

Section: Egf-receptor Tyrosine Kinase Inhibitor Inhibits In Vitro Endmentioning

confidence: 99%

See 1 more Smart Citation

Selective and Specific Activation of Rab5 during Endocytosis of Receptor Tyrosine Kinases

Jozic¹

View full text Add to dashboard Cite

The Rab family of proteins are low molecular weight GTPases that have the ability to switch between GTP-(active) and GDP-(inactive) bound form, and in that sense act as molecular switches. Through distinct localization on various vesicles and organelles and by cycling through GTP/GDP bound forms, Rabs are able to recruit and activate numerous effector proteins, both spatially and temporally, and hence behave as key regulators of trafficking in both endocytic and biosynhtetic pathways. The Rab5 protein has been shown to regulate transport from plasma membrane to the early endosome as well as activate signaling pathways from the early endosome. This dissertation focused on understanding Rab5 activation via endocytosis of receptor tyrosine kinases (RTKs).First, tyrosine kinase activity of RTKs was linked to endosome fusion by demonstrating that tyrosine kinase inhibitors block endosome fusion and activation of Rab5, and a constitutively active form of Rab5 is able to rescue endosome fusion. However, depending on how much ligand is available at the cell surface, the receptor-ligand complexes can be internalized via a number of distinct pathways. Similarly, Rab5 was activated in a ligand-dependent concentration dependent manner via clathrin-and vii caveolin-mediated pathways, as well as a pathway independent of both. However, overexpression Rabex-5, a nucleotide exchange factor for Rab5, is able to rescue activation even when all of the pathways of EGF-receptor internalization were blocked.Next, the three naturally occurring splice variants of Rabex-5 selectively activated Rab5.Lastly, Rabex-5 inhibits differentiation of 3T3-L1 and PC12 cells through 1) degradation of signaling endosome via Rab5-dependent fusion with the early endosome, 2) and inhibition of signaling cascade via ubiquitination of Ras through the ZnF domain at the N-terminus of Rabex-5.In conclusion, these data shed light on complexity of the endosomal trafficking system where tyrosine kinase activity of the receptor is able to affect endosome fusion; how different endocytic pathways affect activation of one of the key regulators of early endocytic events; and how selective activation of Rab5 via Rabex-5 can control adipogenesis and neurogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Egf-receptor Tyrosine Kinase Inhibitor Inhibits In Vitro Endmentioning

confidence: 99%

Selective and Specific Activation of Rab5 during Endocytosis of Receptor Tyrosine Kinases

Jozic¹

View full text Add to dashboard Cite

show abstract

Analysis of tyrphostin AG1478 effect on behavior of internalized EGF receptor at different stages of endocytosis

Cited by 1 publication

References 11 publications

Selective and Specific Activation of Rab5 during Endocytosis of Receptor Tyrosine Kinases

Selective and Specific Activation of Rab5 during Endocytosis of Receptor Tyrosine Kinases

Contact Info

Product

Resources

About