Development requires activation but not phosphorylation of β1 integrins

  1. Yuliya Pylayeva1,2,4 and
  2. Filippo G. Giancotti1,3
  1. 1 Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA;
  2. 2 Sloan-Kettering Division, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, New York, USA

This extract was created in the absence of an abstract.

Named after the ability of many of them to “integrate” the extracellular matrix with the intracellular cytoskeleton, integrins are well-characterized mediators of cellular adhesion and signaling (Giancotti and Ruoslahti 1999; Hynes 2002). Each integrin consists of an α and a β subunit and binds to a distinct, but often overlapping, spectrum of ligands. Whereas β1 integrins mediate cell adhesion to extracellular matrix components, β2 integrins play key roles in immune cell recognition and activation by interacting with counterreceptors of the Ig superfamily, and αIIbβ3 orchestrates platelet aggregation by binding to the polyvalent blood protein fibrinogen. Genetic studies using mouse models have demonstrated that β1 integrins have unique roles in embryonic development, hematopoiesis, wound healing, and cancer (Brakebusch et al. 1997; Grose et al. 2002; White et al. 2004). Successful execution of a number of physiological processes requires precisely choreographed changes in the activity of several integrins. The regulation of integrin functions is complex, and recent studies suggest that it hinges on long-range structural changes, which are propagated across the plasma membrane in both directions (Hynes 2002). In spite of its importance, genetic analysis of this aspect of integrin function has lagged behind. A new paper by Chen et al. (2006), published in the April 15 issue of Genes and Development, intends to remedy this imbalance.

Many integrins are maintained in a default low-affinity state and, hence, need to be activated to exert their function. The past decade has seen the emergence and consolidation of two major paradigms for integrin activation and signaling. The first describes the process through which cytoplasmic signals trigger integrin activation (“inside-to-outside” integrin signaling) (Ginsberg et al. 1992). Most, perhaps all, activating signals promote the binding of talin to the cytoplasmic portion of the integrin β subunit (Liddington and Ginsberg 2002). Talin binding promotes …

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