title: Phosphorylation of the SRC epithelial substrate Trask is tightly regulated in normal epithelia but widespread in many human epithelial cancers.
abstract: OBJECTIVE
  The frequently elevated activities of the c-src and c-yes products in human epithelial tumors suggest that these activated tyrosine kinases have tumorigenic functions analogous to the v-src and v-yes oncogene products. Studies of v-src-transformed fibroblasts have identified many of the effectors of this potent oncogene; however, because c-src and c-yes lack the mutational and promiscuous activities of their retroviral oncogene homologues, their presumptive tumorigenic functions in human epithelial tumors are more subtle, less well-defined, and await identification of possible effectors more directly relevant to epithelial cells.
  
  
  METHODS
  We recently identified a transmembrane glycoprotein named Trask that is expressed in epithelial tissues but not fibroblasts and is phosphorylated by SRC kinases in mitotic epithelial cells. In this study, we have surveyed the expression and phosphorylation of Trask in many human epithelial cancer cell lines and surgical tissues and tumors.
  
  
  RESULTS
  Trask is widely expressed in human epithelial tissues, but its phosphorylation is tightly regulated and restricted to detached mitotic cells or cells undergoing physiologic shedding. However, abberant Trask phosphorylation is seen in many epithelial tumors from all stages including preinvasive, invasive, and metastatic tumors. Trask phosphorylation requires SRC kinases, and is also aberrantly hyperphosphorylated in the SRC-activated PyMT mouse epithelial tumors and dephosphorylated by the SRC inhibitor treatment of these tumors.
  
  
  CONCLUSIONS
  The widespread phosphorylation of Trask in many human epithlelial cancers identifies a new potential effector of SRC kinases in human epithelial tumorigenesis.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California 94143-0875, USA.
authors.forename: Ching Hang
authors.initials: CH
authors.lastname: Wong
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Baehner
authors.forename: Danislav S
authors.initials: DS
authors.lastname: Spassov
authors.forename: Deepika
authors.initials: D
authors.lastname: Ahuja
authors.forename: Donghui
authors.initials: D
authors.lastname: Wang
authors.forename: Byron
authors.initials: B
authors.lastname: Hann
authors.forename: Jimmy
authors.initials: J
authors.lastname: Blair
authors.forename: Kevan
authors.initials: K
authors.lastname: Shokat
authors.forename: Alana L
authors.initials: AL
authors.lastname: Welm
authors.forename: Mark M
authors.initials: MM
authors.lastname: Moasser