Protein tyrosine phosphatase Cytoplasmic

The receptor-like protein tyrosine phosphatases have a transmembrane and, in some cases, a large extracellular domain with a very variable structme (Fig. 8.16). Many, but not all, membrane protein tyrosine phosphatases have two catalytic domains in the cytoplasmic region. The complete structme is very similar to the structure of transmembrane receptors. Understanding of their function is far from complete. Both the natural ligands and the substrate proteins following in the sequence are incompletely characterized. Several studies have demonstrated a role for receptor-like PTPs in neuronal cell adhesion signaling pathways. In cells of the neural tissue, a surface protein, contactin has been identified as ligand for the extracellular domain of a protein tyrosine phosphatase (Peles et al., 1995). 

Fig. 8.16. Domain structure of protein tyrosine phosphatases. Linear representation of functional domains of the transmembrane tyrosine phosphatase CD45 and some cytoplasmic tyrosine phosphatases.

Cytoplasmically localized protein tyrosine phosphatases have a catalytic domain and other structural elements that specify the subcellular localization and association with effector molecules. These structural elements contain sequence signals for nuclear localization, for membrane association and for association with the cytoskeleton (see Fig. 8.16). The presence of SH2 domains suggests that these molecules might interact with signaling pathways involving growth hormones and receptor tyrosine kinases. 

Signal transduction via the receptor-like CD 45 protein tyrosine phosphatase in cells of the blood forming system requires its intracellularly localized phosphatase activity. The cytoplasmic tyrosine kinases p56 " and p59 are thought to be cellular substrates... 

The subcellular localization of protein tyrosine phosphatases is an important aspect of their function. The sequences of cytoplasmic protein tyrosine phosphatases frequently demonstrate sequence signals specifying a particular subcellular localization. This ensures that protein tyrosine phosphatases are only active at defined subcellular sites. The presence of SH2 domains in cytoplasmic protein tyrosine phosphatases also shows that these are coupled, via SH2-phosphotyrosine interactions, to specific substrates, where they then perform their actual function. 

McMahon HT, Rosenthal L, Meldolesi J et al (1990) a-Latrotoxin releases both vesicular and cytoplasmic glutamate from isolated nerve terminals. J Neurochem 55 2039 17 Meathrel K, Adamek T, Batt J et al (2002) Protein tyrosine phosphatase sigma-deficient mice show aberrant cytoarchitecture and structural abnormalities in the central nervous system. J Neurosci Res 70 24-35... 

The best-studied protein tyrosine phosphatases are the high molecular weight cytoplasmic enzymes of the FTP family. X-ray structures of the human FTP IB cytosolic tyrosine phosphatase, have been solved by David Barford et and that of a Yersinia tyrosine phosphatase by Fauman et In Fig. 3.9a and b the structures of the... 

Many members of this class of receptors have an enzymatic activity known as a protein tyrosine kinase within their cytoplasmic segment. This kinase phosphorylates tyrosine residues in the receptors themselves (autophosphory lation), and in other proteins to initiate biochemical cascades. Phosphorylatipn of tyrosine can be reversed by protein tyrosine phosphatases, which are also present in all cells (Shenolikar and Naim, 1990). Tyrosine phosphatases form a diverse family of proteins, some of which are cytosolic while others are transmembrane molecules analogous to receptors. Some members of the transmembrane class may be involved in the mechanism of bacterial and viral infections (Tonks, 1991). Thus, kinases and phosphatases together act as on-off switches in the a ctivation of receptors and other proteins. 

Bourdeau A, Dube N, Tremblay ML (2005) Cytoplasmic protein tyrosine phosphatases, regulation and function the roles of PTPIB and TC-PTP. Curr Opin Cell Biol 17 203-209... 

Some transmembrane receptors have cytoplasmic protein phosphatase activity. Soluble protein phosphatases, such as calcineurin, PP1, PP2A, PP2C, and protein tyrosine phosphatases, also mediate intracellular signals. 

Proteins do not need to be metalloproteins to interact with cadmium, and the proteins with reactive cysteines described in Section 4.2.1 are examples of non-metalloproteins interacting with cadmium. In addition, some proteins that are not recognized as metalloproteins bind zinc extremely tightly. For example, the cytoplasmic domain of receptor protein tyrosine phosphatase p binds zinc with a value of 27 pM [109]. Cadmium is expected to bind tightly to these sites. Significantly, the widespread use of CdCl2 in crystallization studies, to prepare heavy metal derivatives and to phase the diffraction data, provides hundreds of protein structures in which Cd " interacts with amino-acid residues, often in positions that are not known to bind cations. 

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