Role of focal adhesion proteins in signal transduction and oncogenesis.
The focal adhesion is a structure that is formed when a cell comes into contact with the extracellular matrix. Originally, the focal adhesion was thought to only provide structural support for the actin-based cytoskeleton of the cell. However, the last decade has yielded considerable information linking various protein components of the focal adhesion to signal transduction pathways. Examples of focal adhesion proteins include the catalytically active p125FAK, SH2-containing tensin, and the multifunctional LIM domain-containing paxillin. The interactions of focal adhesion proteins may be altered after cellular transformation. This review details how certain focal adhesion proteins are associated in cellular signaling as well as transformation. The importance of various GTP-binding proteins in interacting with and forming the focal adhesion, and the influence they have on neoplastic transformation, are discussed. A key feature of this review is how oncogenes and their respective oncoproteins affect the focal adhesion. Classically, v-src transformation of adherent cells has been studied to characterize focal adhesions, namely, because of the distinct morphological changes that occur in the focal adhesion concomitantly with src transformation. Similarly, the BCR/ABL oncogene, which causes chronic myelogenous leukemia, leads to adhesion defects and can alter the properties of focal adhesion proteins. Thus, we describe some of the relevant interactions between the focal adhesion and the Src and BCR/ABL oncoproteins, respectively.
Weisberg
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E
Division of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Sattler
M
M
Ewaniuk
D S
DS
Salgia
R
R
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016391:Genes, src; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction; D014178:Translocation, Genetic
D015815:Cell Adhesion Molecules; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human