 |
|
|
|
|
|
| | | www.calbiochem.com/adhesion | | | Cell adhesion molecules (CAM) are multi-functional proteins involved in a number of regulatory processes, including cell growth, differentiation and proliferation, migration, and regeneration (Figure 1). Cell adhesion is crucial in the formation and maintenance of coherent multicellular structures. Two major types of cell adhesion processes are seen in multicellular organisms: cell-cell adhesion, where physical bonds are formed between adjacent cells; and cell-matrix adhesion, where cells bind to adhesive proteins in the extracellular matrix.
Cells detect their extracellular milieu via interactions with cell adhesion molecule (CAM) components via integrins and syndecan molecules and with adjacent cells via cadherins, selectins, and the members of the Ig-CAM family. Several adhesion molecules share similar structural features. The adhesive domains in fibronectins and immunoglobin (Ig) type adhesion proteins are structurally related and serve as building blocks in many adhesion proteins. Fibronectins also serve as ligands for the integrin family of adhesion receptors. They contain multiple repeats of 90 amino acid domains known as fibronectin type III (FN III) domains which possess the Arg-Gly-Asp (RGD) cell attachment site. Ig domains that are commonly found in cell-cell adhesion molecules are often found together with FN III domains. Some adhesion molecules, such as N-CAM, may contain both Ig and FN III domains.
The main families of adhesion receptors connect to the cytoskeleton inside the cell. Following their interaction with the ligand, adhesion receptors cluster in regions called focal adhesions. Adhesion receptors also function as signaling molecules. Focal adhesions are rich in tyrosine phosphorylated proteins that couple cell adhesion to signal transduction pathways in the cell. Various adhesion receptors are closely linked to protein kinases and phosphatases.
Integrins are transmembrane heterodimeric receptors composed of noncovalently associated a- and b-subunits. About 20 integrins have been identified thus far. A variety of integrins are shown to support adhesion-dependent growth factor-activation of MAP kinase. Ligand binding to integrin leads to the assembly of focal adhesion which induces tyrosine phosphorylation of a number of cytoskeletal components and signaling molecules. A number of protein tyrosine kinases are activated in focal adhesion as a result of integrin ligation. Focal adhesion kinase (FAK) is activated through autophosphorylation when cells attach through integrin. It is then phosphorylated by src kinase. A number of other signaling molecules subsequently bind to FAK and are phosphorylated, including Grb2, which links FAK to the Ras pathway, and the 85 kDa subunit of the PI 3-kinase (Figure 2). Thus, FAK is a key component in the assembly of focal contact structures that can influence cytoskeletal organization and signal transduction.
Cell adhesion receptors cooperate closely with growth factor receptors through physical linkages between them. For example, integrin avb3 is reported to associate closely with insulin receptor substrate-1, which is a cytoplasmic signal transduction mediator of insulin and IGF receptors. C-CAM, a member of the Ig superfamily, becomes phosphorylated on tyrosine in insulin-stimulated hepatocytes. N-CAM and L-1 and N-cadherin can activate FGF receptor and serve as pseudoligands for the FGF receptor, binding to it at recognition sequences that resemble their own recognition sites.
| | | | | |
|
 |
|
|
