P130 is a membrane-localized glycoprotein and associates
with both SHP-1 and SHP-2. (A) SHP-1–P130 complex localizes to the
membrane compartment. BAC1.2F5 cells were starved of CSF-1 for 20
h and then stimulated with 2,000 U of CSF-1 per ml for 1 min (+) or
left unstimulated (−). Cells were fractionated as described in
Materials and Methods, and aliquots of the P1, P100, and S100 fractions
were immunoprecipitated (IP) with anti-SHP-1 (αSHP-1) or anti-CSF-1R
antibodies. Immune complexes were analyzed by SDS-PAGE (10% gel) and
anti-pTyr immunoblotting. The anti-SHP-1 antibodies used for this panel
are weakly cross-reactive with SHP-2, accounting for the 70-kDa
phosphotyrosyl species; SHP-1-specific reagents are used in all
subsequent experiments. Whole-cell lysates (WCL) and each fraction also
were analyzed. Blots were reprobed with an anti-SHP-1 MAb to test for protein levels,
and blots of each fraction were reprobed with anti-MAPK to monitor
contamination of the P1 and P100 fractions with soluble cytoplasmic
proteins. The positions of migration of Gibco BRL protein molecular
size standards are shown in kilodaltons at the left. (B) P130 is a
glycoprotein. Anti-SHP-1 immunoprecipitates from randomly growing
BAC1.2F5 cells were treated with endo F as described in Materials and
Methods. Deglycosylated (+) and untreated (−) samples were analyzed by
SDS-PAGE (8% gel) and anti-pTyr immunoblotting (left panel). Lectin
binding assays (right panel) were carried out as described in Materials
and Methods, using A. hypogaea lectin (AHL), L.
culinaris lectin (LCL), concanavalin A (ConA), or wheat germ
agglutinin (WGA). Bound proteins were analyzed by SDS-PAGE (8% gel)
and anti-pTyr immunoblotting. An anti-SHP-1 immunoprecipitate was
loaded as a control (Ctrl IP). (C) P130 can coimmunoprecipitate with
SHP-1 and SHP-2. Specific antibodies to SHP-1 and SHP-2 were used in
consecutive immunoprecipitations from the lysates of a randomly growing
normal macrophage cell line (N). Bound proteins were analyzed by
SDS-PAGE (8% gel) and anti-pTyr immunoblotting. The migration of
molecular size standards is indicated in kilodaltons at the left.