| Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I-dependent mitogenic signaling in vascular smooth muscle cells. | |
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MedLine Citation:
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PMID: 20521079 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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In vascular smooth muscle cells, IGF-I stimulates SHPS-1/SHP2/Src complex formation which is required for IGF-I-stimulated cell proliferation. Using SHP2/Src silencing and a Pyk2/Y402F mutant, we showed that Pyk2 was also recruited to the SHPS-1 complex. Pyk2 recruitment to SHPS-1 is mediated via the interaction of Pyk2 Tyr402 and the Src in response to IGF-I. Following Src/Pyk2 association, Src phosphorylates Pyk2 on Tyr881 providing a binding site for Grb2. Cells expressing Pyk2/Y881F showed decreased Grb2 recruitment to SHPS-1 and impaired Shc/Grb2 association. This change led to reduced Erk1/2 (MAP kinase) activation and cell proliferation in response to IGF-I. Our results show that, following its recruitment to the SHPS-1 signaling complex, Pyk2 localizes Grb2 in close proximity to Shc thereby facilitating Shc/Grb2 association which leads to Erk1/2 activation in response to IGF-I. Thus, Pyk2 recruitment to SHPS-1 plays an important role in regulating the IGF-I-stimulated mitogenic response. |
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Authors:
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Xinchun Shen; Gang Xi; Yashwanth Radhakrishnan; David R Clemmons |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-03 |
Journal Detail:
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Title: Cellular and molecular life sciences : CMLS Volume: 67 ISSN: 1420-9071 ISO Abbreviation: Cell. Mol. Life Sci. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9705402 Medline TA: Cell Mol Life Sci Country: Switzerland |
Other Details:
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Languages: eng Pagination: 3893-903 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of North Carolina, Chapel Hill, 27599, USA. |
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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AG022331/AG/NIA NIH HHS; HL56850/HL/NHLBI NIH HHS |
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