Intracellular cell adhesion molecules

Many transmembrane proteins that mediate intracellular signaling form complexes with both intra- and extracellular proteins. For example, neural cell adhesion molecules (NCAMs) are cell-surface glycoproteins (Ch. 7). The extracellular domains of NCAMs can activate fibroblast growth factor receptors when clustered by reaction with NCAM antibodies [4] or by homotypic binding to domains of adjacent cells (see Fig. 7-2). Activation was found to sequester a complex of NCAM, (31 spectrin and PKC(32 into rafts, as defined by the operational criteria discussed on p. 28. 

SECs, like the vascular endothehum, play an active part in the control of leucocyte recruitment in cases of acute and chronic inflammatory conditions. Eeucocyte recruitment from the blood compartment is a crucial determinant for the induction of immunity and inflammation. SECs control this process by producing cytokines that activate leucocytes and by expressing adhesion molecules. Under inflammatory conditions upregulation of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was found [35 36], as well as expression of E-selectin and P-selectin [37]. Together with the expression of CD4 on SECs it has been postulated that these adhesion molecules might also be involved in the adhesion of KC cells to the sinusoidal wall [20]. 

There are multicellular interactions that are important in inflammatory processes and in vascular remodeling. Activated platelets induce endothelial cells to secrete chemokines and to express adhesion molecules, indicating that platelets could initiate an inflammatory (Table I) response of the vessel wall. Activated platelets promote leukocyte binding to inflamed or atherosclerotic lesions (27,28). Cell adhesion molecules (CAMs) are responsible for leukocyte-endothelium interactions. It plays a crucial role in inflammation and atherogenesis. Vascular CAM-1 (VCAM-I)and intracellular CAM-1 (ICAM-I) promote monocyte recruitment to sites of injury and constitute a critical step in inflammation and in atherosclerotic plaque development. TSP-1, a matricellular protein released in abundance from activated platelets and accumulated in sites of vascular injury, induces the expression of VCAM-1 and ICAM-1 on endothelium and significantly increases the monocyte attachment (29). 

Many mediators of inflammation have been identified— cytokines IL-6, tumor necrosis factor alpha cell adhesion molecules intracellular adhesion molecule-1 (ICAM-I), P-selectin and acute phase reactants CR.R fibrinogen, serum amyloid A, and soluble CD40 (Fig. I) (3). Myeloperoxidase is an enzyme secreted from monocytes, neutrophils, and macrophages. A single measurement taken from patient with chest pain in the emergency department predicted the early risk of myocardial infarction and the risk of major cardiac of ends in the next 30 days to six months (15). 

Epithelial cadherin (E-cadherin) has a molecular weight of 130 kDa and is found in PNS myelin. E-cadherin is a protein of the superfamily of calcium-dependent cell adhesion molecules that can usually form adherent junctions. This protein has an N-terminal extracellular domain, a short transmembrane domain and a C-terminal intracellular domain. 

Most of the IL-1 activity in plasma is from IL-lp, IL-la existing mainly in an intracellular or membrane-associated IL-1 shares many of its functions with TNF, but important differences between IL-1 and TNF exist. For example, IL-1 is in general not toxic, and TNF is a potent cytotoxic effector (see the Biological Actions of TNF section). One of their shared functions is the induction of expression of the vascular cell adhesion molecule (VCAM) by endothelial cells. Studies have indicated that TNF may be more important than IL-1 in induction of VCAM expression at least in the nasal mucosa. ... 

Isom Yes. The reason we went after that is because in the LI family of cell adhesion molecules an intracellular tyrosine residue is critical for cell adhesion and ankyrin recruitment. We predict that the tyrosine in will be very important in formation of the Na channel signalling complex (Malhotra et al 2001). 

PTG. finally, the PTG includes several classes of molecules whose therapeutic potential is only now being realized, such as both intracellular and extracellular kinases and phosphatases, as well as cell adhesion molecules. These classes of targets represent over 1000 potential novel points of intervention for chronic disease management The size of each protein family, and their distribution according to target type, is presented in Pig. 4.3. 

Cell-Adhesion Molecules Bind to One Another and to Intracellular Proteins... 

Forscher and Smith, 1988). In this view, any molecule on the membrane of the growth cone that takes part in a receptor-ligand interaction leading to intracellular changes of the type referred to above could be considered to be an axon guidance molecule - a definition that encompasses a far wider variety of molecules than those traditionally considered to be cell adhesion molecules. 

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