Ligands and Signaling Through Receptor‐Type Tyrosine Phosphatases

Abstract

SummaryVirtually every aspect of cellular proliferation and differentiation is regulated by changes in tyrosine phosphorylation. Tyrosine phosphorylation, in turn, is controlled by the opposing activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). PTKs are often transmembrane proteins (receptor PTKs) whose enzymatic activities and signaling functions are tightly regulated by the binding of speci c ligands. A variety of transmembrane PTPs has also been identi ed; these proteins are called receptor PTPs (RPTPs), but in most cases their roles as receptors are very poorly understood. This review discusses the evidence that RPTPs are actually receptors for extrinsic ligands, and the extent to which interactions with putative ligands are known or suspected to cause changes in enzymatic activity. Finally, some of the RPTP substrates believed to be physiologically important are described. The evidence gathered to date suggests that models derived from studies of receptor PTKs may be too simple to account for the diversity and complexity of mechanisms through which ligand binding controls RPTP function.

Receptor Tyrosine Phosphatases Guide Vertebrate Motor Axons during Development

“…More progress has been made in the discovery of potential substrates for LAR; it can act together with Abl to coordinate phosphorylation/dephosphorylation of the profilin-interacting protein Ena. Additionally, LAR interacts with the guanine nucleotide exchange factor Trio, which can activate Rho family GTPases to regulate actin filaments (Bixby, 2001;Johnson and Van Vactor, 2003). A recent paper shows that PTP-␦ interacts with an actin-binding protein called MIM in fibroblasts, suggesting that cytoskeletal interactions are common to type IIa RPTPs (Gonzalez-Quevedo et al, 2005).…”

Distinct PTPmu-associated signaling molecules differentially regulate neurite outgrowth on E-, N-, and R-cadherin

“…The PTPμ specific WPTPμ-Tat peptide sequence (Xie et al, 2006) corresponds to the HLH wedge shaped sequence (Hoffmann et al, 1997), located in the juxtamembrane domain of PTPμ near the D1 catalytic domain. By mimicking PTPμ inter/intramolecular interactions that regulate catalytic activity of the phosphatase (Bixby, 2001; Brady-Kalnay, 2001; Ensslen-Craig and Brady-Kalnay, 2004), it has been proposed that the WPTPμ-Tat peptide regulates PTPμ function or catalytic activity (Xie et al, 2006). Each peptide includes a Tat-derived domain linked to the C terminus, which allows for uptake of the peptide into the cell.…”

A Novel Substrate of Receptor Tyrosine Phosphatase PTPRO Is Required for Nerve Growth Factor-Induced Process Outgrowth

“…Cas , and regulators of small GTP proteins such as GIT-1, an Arf-GAP, and Trio, a Rho-guanine nucleotide exchange factor (Bixby, 2001;. In the case of type III RPTPs, the PDGF receptor, the HGF receptor, and p120 ctn have been identified as substrates for the hematopoietic RPTP known as DEP-1/CD148 (Kovalenko et al, 2000;Holsinger et al, 2002;Palka et al, 2003).…”