Accession Number:

ADA408725

Title:

Mechanism of Ras Activation by TGFBeta

Descriptive Note:

Annual rept. 1 Jul 2001-30 Jun 2002

Corporate Author:

PENNSYLVANIA STATE UNIV HERSHEY COLLEGE OF MEDICINE

Personal Author(s):

Report Date:

2002-07-01

Pagination or Media Count:

123.0

Abstract:

We have shown that TGW beta regulates Has and Mapk signaling pathways. Dynein is a molecular motor protein that mediates intracellular transport of cargo along polarized microtubules MTs toward the minus ends. Activation of a motor may occur by several mechanisms, which can be regulated by growth factors. Thus, the receptors and signaling pathways for these polypeptides are potential mediators of motor protein activation and organelle trafficking, events which ultimately determine the collective spatial organization of the signaling pathways within the cell. Here we describe a novel TGF beta receptor-interacting protein, termed km23, which is also a dynein light chain. km23 interacts with TGF beta receptors and is phosphorylated after ligand-receptor engagement forced expression of km23 induces specific TGF beta responses. TGF beta induces the recruitment of km23 to the intermediate chain of dynein, which is blocked by a kinase-deficient form of TGF beta RII. This is the first demonstration of a link between dynein and a natural, growth inhibitory cytokine. Further, our results indicate km23 may function as a motor receptor for the recruitment and transport of TGF beta signaling components along MTs. Alterations in km23 would alter such transport and disrupt TGF beta growth inhibitory signals, thereby increasing the malignant behavior of the cells.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE