PTPζ cleavage. The PTPζ-A and –B isoforms are cleaved in a similar manner. For simplicity’s sake, cleavage of PTPζ-B is shown. The ECD of PTPζ-B consists of a CA domain, an FNIII repeat, and a unique spacer region. S1 cleavage by either MMP-9 or ADAM-17 at the plasma membrane (PM), yields an 180kDa shed ZB-ECD [30]. S2 cleavage by γ-secretase yields the 73kDa ZB-ICD, which is found both in the cytosol and nucleus [30]. Molecular diagnostics, indicated by the magenta stars, could be developed to bind to the contactin1-binding site in the CA domain [78], the NgCAM, NCAM, NrCAM binding site in between the CA and FNIII repeat [20], the tenascin binding site in the FNIII repeat [70], or the pleiotrophin binding site in the spacer region [24].