A guide to signaling pathways connecting protein-glycan interaction with the emerging versatile effector functionality of mammalian lectins

The plasma membrane establishes the interface for the communication of cells with the environment. Thus, surface determinants govern the reactivity and capacity of cells to respond to external signals. Changes in their profile, for example in malignant transformation, and manifestation of cell-type-specific features apparently hold inspiring lessons in store for us on how they are translated into cellular responses. But before turning to the signaling routes the biochemical modes for coding signals warrant a comment, as proteins are often unduly portrayed as the decisive hardware. In contrast, and actually prominent among the biochemical systems to store information, carbohydrate epitopes of cellular glycoconjugates favorably combine high-density coding with strategic positioning, rendering them readily accessible for interactions with adaptor molecules. The interaction with lectins is the ignition key to start glycoconjugate-mediated biosignaling. Several plant lectins, especially due to their mitogenicity, have become a popular type of laboratory tool to elicit cell responses and to analyze biochemical pathways leading from initial binding to measured activity such as enhanced proliferation. With emerging insights into the roles of mammalian (endogenous) lectins and the promising perspective for medical applications, emphasis in this area is shifting from model studies with plant proteins toward work with the physiological effectors. By targeting branch-end epitopes of glycan chains two classes of endogenous lectins, i.e. galectins and selectins, are remarkably well suited to establish initial contacts with the cell surface. Indeed, these lectins - in their interplay with certain cognate binding partners - are being defined as potent signal inducers. Consequently, we can take aspects of their activity profiles as incentive to dissect underlying routes of signal transmission with an eye more on principles than on intricate case-specific details. Hence, regulation of cell growth by cascades of mitogen-activated protein kinases (MAPKs), cyclins/cyclin-dependent kinases and inhibitors thereof, of cell survival by the phosphatidylinositol 3'-OH kinase (PI3K)/Akt pathway, the remodeling of the cytoskeleton by integrin-mediated cell adhesion, the implication of p53 in regulating cell fate and details of programmed cell death by the intrinsic and extrinsic routes for induction of apoptosis will be discussed. Moreover, we will look at selectin-induced signaling during leukocyte homing. Explicitly, it is the aim of our review to familiarize glycoscientists, whose main interest is to scrutinize the structural aspects or to develop applications, with basic concepts of cellular signaling triggered by these interactions.