Shf, a Shb-like adapter protein, is involved in PDGF-alpha-receptor regulation of apoptosis.
Recent work has implicated the importance of adapter proteins in signal transduction. To identify homologues of the previously identified adapter protein Shb, database searches were performed. A Shb-like protein was found which we have named Shf. Shf contains an SH2 domain and four putative tyrosine phosphorylation sites and is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. The SH2 domain of Shf bound to the PDGF-alpha-receptor at tyrosine-720, but not to the PDGF-beta-receptor in PAE cells. Pervanadate induced tyrosine phosphorylation of Shf in NIH3T3 fibroblasts overexpressing this protein, whereas PDGF-AA alone had no detectable effect. NIH3T3 cells overexpressing Shf displayed significantly lower rates of apoptosis than control cells in the presence of PDGF-AA. Our findings suggest a role for the novel adapter Shf in PDGF-receptor signaling and regulation of apoptosis.
Lindholm
C K
CK
Department of Medical Cell Biology, Uppsala University, Uppsala, S-75123, Sweden.
Frantz
J D
JD
Shoelson
S E
SE
Welsh
M
M
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014638:Vanadates / Q000494:pharmacology; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C490081:SHB protein, human; C417258:SHF protein, human; C085634:Shb protein, mouse; C076715:pervanadate; C075278:platelet-derived growth factor A; D019000:Phosphotyrosine; D014638:Vanadates; D020796:Receptor, Platelet-Derived Growth Factor alpha