Identification of SH2-B as a signaling molecule for growth hormone, platelet-derived growth factor and nerve growth factor.
Rui, Liangyou
1998
Abstract
Polypeptide hormones and growth factors regulate a variety of vital activities via binding and activating their cognate cell surface receptors which in turn recruit intracellular signaling molecules and transmit signals inside cells. In this dissertation, SH2-B is identified as an important intracellular signaling protein for growth hormone (GH), platelet-derived growth factor (PDGF) and nerve growth factor(NGF). SH2-B was found to be phosphorylated in response to GH, PDGF and NGF. However, the mechanisms by which SH2-B was phosphorylated are different among these polypeptide hormones and growth factors. GH stimulates activation of JAK2, and promotes association of SH2-B with JAK2 and tyrosyl phosphorylation of SH2-B by JAK2 in 3T3-F442A fibroblasts. PDGF stimulates the binding of SH2-B directly to tyrosyl phosphorylated PDGF receptor, and promotes the phosphorylation of SH2-B on both tyrosines and serines and/or threonines in 3T3-F442A and NIH3T3 cells. NGF stimulates phosphorylation of SH2-B predominantly on serines and/or threonines via a MEK-dependent pathway in PC12 cells. SH2-B was found to play an essential role in PDGF-induced actin rearrangement including membrane ruffling, and is required for NGF-induced neurite outgrowth in which actin cytoskeletal rearrangement is thought to be a driving force. The SH2 domain of SH2-B was found to be vital for SH2-B binding to JAK2 and PDGF receptor as well as for its phosphorylation by JAK2 and NGF stimulation. The SH2 domain is also required for the action of SH2-B in GH- and PDGF-stimulated membrane ruffling and NGF-induced neurite outgrowth. These data indicate that SH2-B is a crucial, previously unknown signaling molecule involved in the regulation of the actin cytoskeleton and cell morphology by polypeptide hormones and growth factors including GH, PDGF and NGF.Subjects
Growth Hormone Identification Molecule Nerve Growth Factor Platelet-derived Growth Factor Sh2-b Signaling
Types
Thesis
Metadata
Show full item recordCollections
Showing items related by title, author, creator and subject.
-
Berger, Paul R.; Chang, Kevin H.; Bhattacharya, Pallab K.; Singh, Jasprit; Bajaj, K. K. (The American Institute of Physics, 1988-08-22)
-
Shimizu, Emi; Saito, Ryoichiro; Nakayama, Youhei; Nakajima, Yu; Kato, Naoko; Takai, Hideki; Kim, Dong‐soon; Arai, Masato; Simmer, James; Ogata, Yorimasa (American Academy of PeriodontologyWiley Periodicals, Inc., 2005-09)
-
Meghani, Mihir A.; Martin, Donna M.; Singleton, J. Robinson; Feldman, Eva L. (Elsevier, 1993-10-20)
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.