Role of SRC homology 2-containing tyrosine phosphatase 2 on proliferation of rat smooth muscle cells.
OBJECTIVE
Src homology 2-containing phosphotyrosine phosphatase 2 (SHP2) is ubiquitously expressed and believed to function as part of a positive signaling pathway mediating growth factor-induced protein tyrosine phosphorylation. Proliferation of aortic vascular smooth muscle cells (SMCs) is an important contributor to atherosclerosis. We examined the effect of SHP2 expression on SMC proliferative activity.


RESULTS
SHP2 was abundant in cultured aortic SMCs, and SHP2 staining was markedly increased in the thickened aortic intima in rats with balloon-induced injury. We obtained several SMC clones by using geneticin screening. Endogenous SHP2 expression varied among individual clones. Significant positive relationships were observed between SHP2 expression and bromodeoxyuridine uptake in SMCs stimulated by FBS, platelet-derived growth factor, or insulin-like growth factor-1. In SMCs transiently transfected with SHP2, FBS stimulation significantly increased bromodeoxyuridine uptake beyond the uptake by control SMCs.


CONCLUSIONS
Increased SHP2 expression in SMCs may accelerate aortic atherosclerosis by increasing cell growth.
Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Japan.
Naoto
N
Seki
Naotake
N
Hashimoto
Yoshifumi
Y
Suzuki
Seijiro
S
Mori
Kimiko
K
Amano
Yasushi
Y
Saito
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001161:Arteriosclerosis / Q000201:enzymology / Q000473:pathology; D015152:Blotting, Northern; D001973:Bromodeoxyuridine / Q000378:metabolism; D002339:Carotid Arteries / Q000033:anatomy & histology; D020212:Carotid Artery Injuries / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY; D014162:Transfection; D017539:Tunica Intima / Q000033:anatomy & histology / Q000473:pathology
D000906:Antibodies; D006133:Growth Substances; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D054648:Protein Phosphatase 2; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; D001973:Bromodeoxyuridine