Receptor Protein Tyrosine Phosphatases, cell-cell adhesion and signal transduction: We are studying the role of receptor protein tyrosine phosphatases (RPTPs) in signals transduced upon cell-cell contact. Some RPTPs such as PTPµ have cell adhesion molecule-like extracellular segments and are involved in adhesion-dependent signaling. PTPµ mediates adhesion by binding homophilically, i.e., PTPµ on the surface of one cell binds to PTPµ on an apposing cell. Interestingly, we found that PTPµ associates with another family of cell adhesion molecules called cadherins. Cadherins are adhesion molecules that play a role in cytoskeletal organization and cell junction formation. We are investigating the role of RPTPs and tyrosine phosphorylation in assembly and signal transduction at sites of cell-cell adhesion.
RPTPs and cancer: We are investigating the role of RPTPs in cell growth and malignancy in cancer. Protein tyrosine kinases can cause uncontrolled cell growth by disrupting the balance of cellular phosphotyrosine levels suggesting that PTPs may play an important role in negative growth regulation or could function as tumor suppressors. In this regard, we have recently found that certain cancer cells have lost PTPµ expression. Therefore, we are determining whether restoration of PTPµ expression in cancer cells results in changes in adhesion, growth, tumorigenicity or metastasis.
RPTPs and development of the nervous system: Cell adhesion is critical to the establishment of proper connections in the nervous system. PTPµ is expressed in the brain and may play a role in neuronal development by sending signals in response to cell adhesion. We demonstrated that PTPµ promotes neurite outgrowth from chick retinal ganglion cells and is found in a complex with N-cadherin in retina. PTPµ is permissive to nasal retinal ganglion cells (movie #1) and is repulsive to temporal retinal ganglion cells (movie #2). PTPµ is expressed by retinal ganglion cells whose axons project via the optic nerve to visual centers in the brain. Nasal and temporal neurons project to different areas in the brain. Retinotectal projection or pathfinding of retinal neurons to the brain may be controlled by PTPµ.
Selected Publications
Craig SE, Brady-Kalnay SM. Cancer Cells Cut Homophilic Cell Adhesion Molecules and Run. Cancer Res. 2010 Nov 17. [PubMed]
Becka S, Zhang P, Craig SE, Lodowski DT, Wang Z, Brady-Kalnay SM.
Characterization of the adhesive properties of the type IIb subfamily receptor protein tyrosine phosphatases. Cell Commun Adhes. 2010 Apr. [PubMed]
Phillips-Mason PJ, Kaur H, Burden-Gulley SM, Craig SE, Brady-Kalnay SM.
Identification of phospholipase C gamma1 as a protein tyrosine phosphatase mu substrate that regulates cell migration. J Cell Biochem. 2010 May 19. [PubMed]
Burden-Gulley SM, Gates TJ, Burgoyne AM, Cutter JL, Lodowski DT, Robinson S,
Sloan AE, Miller RH, Basilion JP, Brady-Kalnay SM. A novel molecular diagnostic of glioblastomas: detection of an extracellular fragment of protein tyrosine phosphatase mu. Neoplasia. 2010 April. [PubMed]
Zhang P, Becka S, Craig SE, Lodowski DT, Brady-Kalnay SM, Wang Z.
Cancer-derived mutations in the fibronectin III repeats of PTPRT/PTPrho inhibit cell-cell aggregation. Cell Commun Adhes. 2009 Dec. [PubMed]
Oblander SA, Brady-Kalnay SM. Distinct PTPmu-associated signaling molecules differentially regulate neurite outgrowth on E-, N-, and R-cadherin. Mol Cell Neurosci. 2010 May;44(1):78-93. Epub 2010 Mar 1. PubMed PMID: 20197094
[PubMed]
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