Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets.

Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets. Research Abstract Details 

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Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets. Abstract Text:

Yi Lu,Hang-Ping Yao,Ming-Hai Wang,Yi Lu,Hang-Ping Yao,Ming-Hai Wang,Yi Lu,Hang-Ping Yao,Ming-Hai Wang,

Aberrant expression of the RON (Recepteur d'Origine Nantais) receptor tyrosine kinase, accompanied by generation of multiple splicing or truncated variants, contributes to pathogenesis of epithelial cancers. Currently, six variants including RONDelta170, Delta165, Delta160, Delta155, Delta110, and Delta55 with various deletions or truncations in the extracellular or intracellular regions have been identified. The extracellular sequences contain functional structures such as sema domain, PSI motif, and IPT units. The deletion or truncation results in constitutive phosphorylation and increased kinase activities. Oncogenic RONDelta160, generated by exclusion of the first IPT unit, is a typical example. In contrast, the deletion adjacent to the conserved MET(1254) in the kinase domain converts RON into a dominant negative agent. Among three mechanisms underlying isoform production, the switch from constitutive to alternative pre-mRNA splicing is the major event in producing RON variants in cancer cells. Most of the RON variants have the ability to activate multiple signaling cascades with a different substrate specificity and phosphorylation profile. They regulate cell migration, invasion, and proliferation, which contribute to the invasive phenotype and promote the malignant progression. Thus, determining the pathogenesis of RON variants is critical in understanding the mechanisms underlying cancer initiation and progression. Targeting oncogenic signals elicited by RON or its variants by special antibody or small interfering RNA could provide a novel strategy for the treatment of malignant epithelial cancers.

Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets. Publishing Authors By Initials

Y Lu,HP Yao,MH Wang,Y Lu,HP Yao,MH Wang,Y Lu,HP Yao,MH Wang,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets. Journal Published:

PUBLICATION TYPE: Review

Journal: Cancer letters

VOLUME: 257

Page Numbers: 157-64

Journal Abbreviation: Cancer Lett.

ISSN: 0304-3835

DAY: 21

MONTH: 09

YEAR: 2007

Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets. Information

Number of References: 52

LANGUAGE: eng

NlmUniqueID: 7600053

Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: drug effects

Chemical & Substance for Abstract: Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets. Information

Substance Name: Receptor Protein-Tyrosine Kinases

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets.

AFFILIATION: Laboratory of Cancer Biology and Therapeutics, Institute of Infectious Diseases at First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, People's Republic of China.

Country: Ireland

AGENCY: United States NCI

GRANT: R01 CA91980

ACRONYM: CA

MEDLINETA: Cancer Lett

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