Receptor protein tyrosine phosphatases as mediators of cellular adhesion.
Receptor protein tyrosine phosphatases (RPTPs) are structurally characterized by the diversity of their extracellular domains (ECDs). These domains display Ig-like, fibronectin type III (FNIII), MAM (meprin, A5, PTPmu), and carbonic anhydrase (CAH) motifs that resemble those present in many cell adhesion molecules (CAMs). However, in contrast to most CAMs, RPTPs also contain an intracellular domain possessing phosphatase activity. This combination makes RPTPs unusual in their ability to directly couple extracellular adhesion mediated events to intracellular signaling pathways. Even though identifying physiologically relevant ligands for RPTPs has proven difficult, recent experiments have shown that RPTPs can bind to themselves (homophilic) as well as to other proteins (heterophilic). For example, the type IIb RPTP, PTPmu? acts as a homophilic cell adhesion protein for epithelial and neural cells while the type V RPTP, PTPbeta/zeta binds a variety of CAMs and ECM components such as N-CAM and pleiotrophin. Interestingly, both PTPmu and PTPbeta/zeta interact with and regulate the tyrosine phosphorylation level of catenins, which are critical in physiological and pathological events such as cell migration, adhesion and transformation. In addition to their role as CAMs, RPTPs directly interact with intracellular adhesion regulators such as the cadherin/catenin complex, p130cas and GIT1. In summary, RPTPs represent a diverse family of transmembrane proteins that act as adhesion receptors and directly translate this engagement into intracellular signaling by modulating phosphotyrosine levels. Discovering the specific roles of RPTPs as receptors and identifying their ligands may lead to a better understanding of human illnesses whose underlying mechanisms involve cellular adhesion.
Beltran
Pedro J
PJ
Department of Pharmacology and Neuroscience Program, University of Miami, Miami, Florida 33136, USA.
Bixby
John L
JL
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*
D020794:Receptor Protein-Tyrosine Kinases