scholarly journals ErbB2 Is Necessary for Induction of Carcinoma Cell Invasion by Erbb Family Receptor Tyrosine Kinases

2000 ◽  
Vol 148 (2) ◽  
pp. 385-397 ◽  
Author(s):  
Kathryn S.R. Spencer ◽  
Diana Graus-Porta ◽  
Jie Leng ◽  
Nancy E. Hynes ◽  
Richard L. Klemke
Keyword(s):  
Cell Migration ◽  
Cell Invasion ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Carcinoma Cell ◽  
Adaptor Proteins ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Erbb Receptor ◽  
Erk Activation

The epidermal growth factor (EGF) family of tyrosine kinase receptors (ErbB1, -2, -3, and -4) and their ligands are involved in cell differentiation, proliferation, migration, and carcinogenesis. However, it has proven difficult to link a given ErbB receptor to a specific biological process since most cells express multiple ErbB members that heterodimerize, leading to receptor cross-activation. In this study, we utilize carcinoma cells depleted of ErbB2, but not other ErbB receptor members, to specifically examine the role of ErbB2 in carcinoma cell migration and invasion. Cells stimulated with EGF-related peptides show increased invasion of the extracellular matrix, whereas cells devoid of functional ErbB2 receptors do not. ErbB2 facilitates cell invasion through extracellular regulated kinase (ERK) activation and coupling of the adaptor proteins, p130CAS and c-CrkII, which regulate the actin-myosin cytoskeleton of migratory cells. Overexpression of ErbB2 in cells devoid of other ErbB receptor members is sufficient to promote ERK activation and CAS/Crk coupling, leading to cell migration. Thus, ErbB2 serves as a critical component that couples ErbB receptor tyrosine kinases to the migration/invasion machinery of carcinoma cells.

scholarly journals Cell migration and invasion in human disease: the Tks adaptor proteins

2012 ◽  
Vol 40 (1) ◽  
pp. 129-132 ◽  
Author(s):  
Sara A. Courtneidge
Keyword(s):  
Cell Migration ◽  
Cell Invasion ◽  
High Throughput Screening ◽  
Tumour Growth ◽  
Control Cell ◽  
Adaptor Proteins ◽  
Migration And Invasion ◽  
Screening Assay ◽  
High Throughput Screening Assay ◽  
Invadopodia Formation

Cell invasion plays a central role in a wide variety of biological phenomena and is the cause of tumour growth and metastasis. Understanding the biochemical mechanisms that control cell invasion is one of the major goals of our laboratory. Podosomes and invadopodia are specialized cellular structures present in cells with physiological or pathological invasive behaviours. These transient structures are localized at the ventral cell surface, contain an array of different proteins and facilitate cell–substrate adhesion, as well as the local proteolytic activity necessary for extracellular matrix remodelling and subsequent cellular invasion. We have shown previously that the adaptor proteins and Src substrates Tks4 and Tks5 are required for podosome and invadopodia formation, for cancer cell invasion in vitro, and for tumour growth in vivo. We have also defined a role for the Tks-mediated generation of ROS (reactive oxygen species) in both podosome and invadopodia formation, and invasive behaviour. Tks4 and Tks5 are also required for proper embryonic development, probably because of their roles in cell migration. Finally, we recently implicated podosome formation as part of the synthetic phenotype of vascular smooth muscle cells. Inhibitors of podosome and invadopodia formation might have utility in the treatment of vascular diseases and cancer. We have therefore developed a high-content cell-based high-throughput screening assay that allows us to identify inhibitors and activators of podosome/invadopodia formation. We have used this assay to screen for small-molecule inhibitors and defined novel regulators of invadopodia formation. In the present paper, I review these recent findings.

scholarly journals Receptor Tyrosine Kinases in Kidney Development

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Renfang Song ◽  
Samir S. El-Dahr ◽  
Ihor V. Yosypiv
Keyword(s):  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Kidney Development ◽  
Receptor Tyrosine Kinases ◽  
Adaptor Proteins ◽  
Downstream Signaling ◽  
Arterial Blood ◽  
Intracellular Signal ◽  
Human Birth

The kidney plays a fundamental role in the regulation of arterial blood pressure and fluid/electrolyte homeostasis. As congenital anomalies of the kidney and urinary tract (CAKUT) constitute one of the most common human birth defects, improved understanding of the cellular and molecular mechanisms that lead to CAKUT is critical. Accumulating evidence indicates that aberrant signaling via receptor tyrosine kinases (RTKs) is causally linked to CAKUT. Upon activation by their ligands, RTKs dimerize, undergo autophosphorylation on specific tyrosine residues, and interact with adaptor proteins to activate intracellular signal transduction pathways that regulate diverse cell behaviours such as cell proliferation, survival, and movement. Here, we review the current understanding of role of RTKs and their downstream signaling pathways in the pathogenesis of CAKUT.

scholarly journals Engineering a single ubiquitin ligase for the selective degradation of all activated ErbB receptor tyrosine kinases

Oncogene ◽  
2013 ◽  
Vol 33 (8) ◽  
pp. 986-995 ◽  
Author(s):  
F Kong ◽  
J Zhang ◽  
Y Li ◽  
X Hao ◽  
X Ren ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Erbb Receptor ◽  
Selective Degradation
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