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Sci. STKE, 9 December 2003
[DOI: 10.1126/stke.2122003tr8]

Growth Factors Bind Receptor Tyrosine Kinases to Stimulate Cell Survival, Cell Division, Cell Growth, and Cytoskeletal Rearrangement

Lewis C. Cantley*

Department of Cell Biology, Harvard Medical School, Division of Signal Transduction, Beth Israel Deaconess Medical Center, 4 Blackfan Circle, Boston, MA 02115, USA.

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*Corresponding author. E-mail, cantley{at}helix.mgh.harvard.edu

Description

These two animations show some of the molecular events associated with the growth factors activation of receptor tyrosine kinases that leads to the stimulation of phosphoinositide 3-kinase (PI3K). The animations are intended to be viewed sequentially starting with Animation 1; however, they can be used to independently to explore different aspects of PI3K signaling. In Animation 1, growth factors stimulate cell survival and entry into the S phase of the cell cycle. In Animation 2, growth factors stimulate the activation of proteins that regulate the cytoskeleton, stimulation of protein synthesis, and stimulation of the Tec family of tyrosine kinases. Animation 2 also shows how the action of phosphatases, such as PTEN, terminates signaling and resets the system to receive a new stimulus. The cellular processes illustrated include protein and lipid phosphorylation and dephosphorylation, protein degradation, protein translocation, and regulation of gene expression. The animations were originally created to accompany the Phosphoinositide 3-Kinase Pathway in the STKE Connections Maps.

Press the green arrowheads to proceed through the animation, or use the buttons at the top of the animation to pause, restart, or move forward through multiple frames.

These animations were created by Cameron Slayden with scientific oversight of L. C. Cantley, Department of Cell Biology, Harvard Medical School.

Animation 1. Phosphoinositide 3-kinase activation stimulates cell survival and proliferation. Growth factors stimulate receptor tyrosone kinases, which results in autophosphorylation of the receptor and recruitment of various binding partners to the receptor. Recruitment and activation of PI3K then results in phosphorylation of the membrane lipids, producing phosphoinositide (3,4,5) triphosphate (PIP3), which is recognized by proteins containing pleckstrin homology (PH) domains. The association of protein kinases, AKT and PDK1, with PIP3 results in activation of AKT, which through activation and inhibition of various downstream targets mediates a cell survival signal and a cell division signal, allowing cells to progress into S phase of the cell cycle.

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Animation 2. Phosphoinositide 3-kinase activation regulates metabolism, the cytoskeleton, and the Tec family kinases. This animation starts after the receptors have been activated and PI3K has been stimulated and AKT and PDK1 have been recruited to the plasma membrane and activation. Some of the molecular events associated with the stimulation of RNA translation and protein synthesis mediated by AKT and PDK1 are illustrated. The accumulation of PIP3 also allows proteins that regulate the cytoskeleton to be recruited to the membrane and activated leading to actin polymerization. PIP3 also triggers the activation of the Tec family of kinases, which through unknown mechanisms contribute to cell growth. Unknown mechanisms of activation or regulation are indicated by question marks.

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Educational Details

Learning Resource Type: Animation

Context: Undergraduate upper division, graduate, professional (degree program)

Intended Users: Teacher, learner

Intended Educational Use: Teach, learn

Discipline: Cell biology, molecular biology

Keywords: Signal transduction, cell survival, PI3 kinase, cell cycle, cytoskeleton, cell growth, translation, gene expression

Technical Details

Format: Shockwave Flash Objects (swf file)

Size: 101 kb (animation 1), 61 kb (animation 2)

Requirements: Macromedia Flash 5 (http://www.macromedia.com/downloads/)

Related Resources

Connections Map: L. C. Cantley, Phosphoinositide 3-kinase pathway. Sci. STKE (Connections Map), http://stke.sciencemag.org/cgi/cm/CMP_6557. [Canonical Pathway]

Connections Map: Morris F. White, Insulin signaling pathway. Sci. STKE (Connections Map), http://stke.sciencemag.org/cgi/cm/stkecm;CMP_12069. [Canonical Pathway]

Review: T. E. Harris, J. C. Lawrence Jr., TOR signaling. Sci. STKE 2003, re15 (2003). [Gloss] [Abstract] [Full Text]

Perspective: T. O. Chan, P. N. Tsichlis, PDK2: A Complex Tail in One Akt. Sci. STKE 2001, pe1 (2001). [Summary] [Full text]

Perspective: J. Montagne, T. Radimerski, G. Thomas, Insulin signaling: Lessons from the Drosophila Tuberous sclerosis complex, a tumor suppressor. Sci. STKE 2001, pe36 (2001). [Summary] [Full Text]

Limits for Use

Cost: Free

Rights: This material may be downloaded, printed, linked to, and/or redistributed without modification for noncommercial, course teaching purposes only, provided credit to STKE is included by listing the citation for the teaching resource.

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Citation: L. C. Cantley, Growth factors bind receptor tyrosine kinases to stimulate cell survival, cell division, cell growth, and cytoskeletal rearrangement. Sci. STKE 2003, tr8 (2003).

© 2003 American Association for the Advancement of Science


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