Src family protein tyrosine kinases are activated following engagement of many different classes of cellular receptors and participate in signaling pathways that control a diverse spectrum of receptor-induced biological activities. While several of these kinases have evolved to play distinct roles in specific receptor pathways, there is considerable redundancy in the functions of these kinases, both with respect to the receptor pathways that activate these kinases and the downstream effectors that mediate their biological activities. This chapter reviews the evidence implicating Src family kinases in specific receptor pathways and describes the mechanisms leading to their activation, the targets that interact with these kinases, and the biological events that they regulate.

Cellular functions regulated by src family kinases

Integrin receptor binding to extracellular matrix proteins generates intracellular signals via enhanced tyrosine phosphorylation events that are important for cell growth, survival, and migration. This review will focus on the functions of the focal adhesion kinase (FAK) protein-tyrosine kinase (PTK) and its role in linking integrin receptors to intracellular signaling pathways. FAK associates with several diAerent signaling proteins such as Src-family PTKs, p130 Cas , Shc, Grb2, PI 3-kinase, and paxillin. This enables FAK to function within a network of integrin-stimulated signaling pathways leading to the activation of targets such as the ERK and JNK/mitogen-activated protein kinase pathways. Focus will be placed on the structural domains and sites of FAK tyrosine phosphorylation important for FAKmediated signaling events and how these sites are conserved in the FAK-related PTK, Pyk2. We will review what is known about FAK activation by integrin receptor-mediated events and also non-integrin stimuli. In addition, we discuss the emergence of a consensus FAK substrate phosphorylation sequence. Emphasis will also be placed on the role of FAK in generating cell survival signals and the cleavage of FAK during caspase-mediated apoptosis. An in-depth discussion will be presented of integrin-stimulated signaling events occurring in the FAK knockout fibroblasts (FAK ˇ ) and how these cells exhibit deficits

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Signaling through focal adhesion kinase

doublecortin, a Brain-Specific Gene Mutated in Human X-Linked Lissencephaly and Double Cortex Syndrome, Encodes a Putative Signaling Protein

Cell adhesion is critical for the genesis and maintenance of both three-dimensional structure and normal function in tissues. The biochemical entities mediating cell adhesion are multiprotein complexes comprising three broad classes of macromolecules: the adhesion receptors, the extracellular matrix

Signal Transduction and Signal Modulation by Cell Adhesion Receptors: The Role of Integrins, Cadherins, Immunoglobulin-Cell Adhesion Molecules, and Selectins

Steven C. Baragona

Papers

NCAM140 Interacts with the Focal Adhesion Kinase p125fak and the SRC-related Tyrosine Kinase p59fyn

rek, a gene expressed in retina and brain, encodes a receptor tyrosine kinase of the Axl/Tyro3 family