Human Receptor Phosphatase

The tyrosine receptor phosphatase PTPRR is composed of an extra cellular region,
a single transmembrane region
and a single intracellular catalytic domain,
which classifies this phosphatase as a receptor class 7 family member.
The mouse homologue(PTPR-SL is predominately expressed in brain
and was shown to regulate activity and cellular localization of MAP kinases.
A 16 amino acid kinase interaction motif (KIM domain) is critical for binding to MAP kinases.

PTPRR has been shown to potently reduce ERK5 kinase activity and
interferes with the translocation of ERK5 into the nucleus.
PTPRR is also a substrate of ERK5.
Phosphorylation by ERK5 reduces affinity of PTPRR for the kinases
but leaves the phosphatase activity unaffected.

The cAMP-dependent protein kinase A (PKA) phosphorylates PTPRR
on a serine residue located in the KIM domain which impairs binding
and dephosphorylation of ERK1/2 and p38.
The rat counterpart PTPBR7 (corresponding to the human alpha form)
is regulated by the nerve growth factor,
which suggests a function of this gene in neuronal growth and differentiation.

Furthermore, antisense studies suggest that loss of expression of the PTPR-BS gamma (-)
isoform result in abnormal patterning of Meckel's cartilage and an increase in the size of the chondrogenic regions.
PTPR-BS gamma may regulate the rate of chondroblast proliferation in the cartilaginous skeleton
in early embryonic development.
So far no disease has been specifically linked to PTPRR;
however, it is expected that since PTPRR acts as a negative regulator
of NGF signalling inhibitors of PTPRR would mimic and facilitate NGF action,
which could be explored in conditions as neurodegenerative diseases of the CNS,
like in Alzheimer's disease.