Macrophage colony-stimulating factor receptor induces tyrosine phosphorylation of SKAP55R adaptor and its association with actin.
The production, survival, and function of monocytes and macrophages are regulated by the macrophage colony-stimulating factor (M-CSF or CSF-1) through its tyrosine kinase receptor. M-CSF receptor activates multiple cytoplasmic pathways in which adaptor and scaffolding proteins play a central role. In this study, we showed that SKAP55-related (SKAP55R) adaptor protein is expressed in myeloid cells and macrophages and is rapidly and transiently tyrosine-phosphorylated in response to M-CSF. M-CSF induced SKAP55R association with other tyrosine-phosphorylated proteins and with actin. When overexpressed in myeloid cells, SKAP55R decreased M-CSF-dependent proliferation without affecting differentiation. Altogether, these results demonstrate that SKAP55R adaptor is implicated in the M-CSF signaling pathway and suggest its role as a negative regulator of growth. Moreover, specific association between SKAP55R and actin support the idea that SKAP55R is implicated in the regulation of actin dynamics under the control of M-CSF.
Bourette
Roland P
RP
Centre de Génétique Moléculaire et Cellulaire, UMR CNRS 5534, Villeurbanne, France. bourette@biomserv.univ-lyon1.fr
Thérier
Julien
J
Mouchiroud
Guy
G
D000199:Actins / Q000737:chemistry / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006133:Growth Substances; D015151:Immunoblotting; D047468:Immunoprecipitation; D007377:Interleukin-3 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry*; D010766:Phosphorylation; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D017077:Culture Media, Conditioned; D006133:Growth Substances; D007377:Interleukin-3; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C116431:src kinase associated phosphoprotein 2; D049452:Green Fluorescent Proteins; D014443:Tyrosine; D016173:Macrophage Colony-Stimulating Factor