RAV12 accelerates the desensitization of Akt/PKB pathway of insulin-like growth factor I receptor signaling in COLO205.

RAV12 accelerates the desensitization of Akt/PKB pathway of insulin-like growth factor I receptor signaling in COLO205. Research Abstract Details 

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RAV12 accelerates the desensitization of Akt/PKB pathway of insulin-like growth factor I receptor signaling in COLO205. Abstract Text:

Jonathan Chi-Hang Li,Ronghao Li,

RAV12 is a high-affinity immunoglobulin G(1) (IgG(1)) chimeric antibody recognizing an N-linked carbohydrate epitope expressed on a number of human carcinomas and adenocarcinomas. RAV12 is efficacious in treating colon, gastric, and pancreatic tumors in xenograft models in vivo. Insulin-like growth factor-I receptor (IGF-IR) is a protein widely overexpressed in tumor-derived cell lines that promotes cell survival and prevents apoptosis. We found the RAV12 epitope (RAAG12) decorated the IGF-IR proteins of RAV12-responsive cell lines such as COLO201, COLO205, and SNU-16. Here, we report findings of IGF-IR signaling manipulation by RAV12. We found that RAV12 caused a significantly accelerated IGF-I-mediated IGF-IR phosphorylation and desensitization in COLO205. We also observed significant changes in some of the major downstream signaling components of IGF-IR. Data suggested that RAV12 treatment accelerated the desensitization of Akt/PKB through IRS1, and such activation could be attenuated by Tyrphostin AG538 (IGF-IR inhibitor), LY294002, or Wortmannin (phosphoinositide-3-kinase inhibitor). Furthermore, RAV12-inhibited IGF-I stimulated COLO205 growth, and the inhibition could be significantly augmented by mitogen-activated protein kinase inhibitor.

RAV12 accelerates the desensitization of Akt/PKB pathway of insulin-like growth factor I receptor signaling in COLO205. Publishing Authors By Initials

JC Li,R Li,

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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RAV12 accelerates the desensitization of Akt/PKB pathway of insulin-like growth factor I receptor signaling in COLO205. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cancer research

VOLUME: 67

Page Numbers: 8856-64

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 15

MONTH: Sep

YEAR: 2007

RAV12 accelerates the desensitization of Akt/PKB pathway of insulin-like growth factor I receptor signaling in COLO205. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

RAV12 accelerates the desensitization of Akt/PKB pathway of insulin-like growth factor I receptor signaling in COLO205. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: metabolism

Chemical & Substance for Abstract: RAV12 accelerates the desensitization of Akt/PKB pathway of insulin-like growth factor I receptor signaling in COLO205. Information

Substance Name: Proto-Oncogene Proteins c-akt

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for RAV12 accelerates the desensitization of Akt/PKB pathway of insulin-like growth factor I receptor signaling in COLO205.

AFFILIATION: Raven Biotechnologies, Inc., South San Francisco, California 94080, USA. jchl@ravenbio.com

Country: United States

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MEDLINETA: Cancer Res

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